Hisashi Oshiro

Immunohistochemical Analysis of Salivary Gland Tumors: Application for Surgical Pathology Practice

Salivary gland tumors are relatively uncommon and there exists a considerable diagnostic difficulty owing to their diverse histological features in individual lesions and the presence of a number of types and variants, in addition to overlapping histological patterns similar to those observed in different tumor entities. The classification is complex, but is closely relevant to the prognostic and therapeutic aspects. Although hematoxylin-eosin staining is still the gold standard method used for the diagnosis, immunohistochemistry (IHC) can enhance the accuracy and be a helpful tool when in cases to investigate the subjects that cannot be assessed by histological examination, such as the cell nature and differentiation status, cell proliferation, and tumor protein expression. This review depicts on the practical diagnostic utility of IHC in salivary gland tumor pathology under the following issues: assessment of cell differentiation, focusing on neoplastic myoepithelial cells; discrimination of histologically mimic tumor groups; diagnosis of specific tumor types, e.g., pleomorphic adenoma, adenoid cystic carcinoma, and salivary duct carcinoma; and evaluation of malignancy and prognostic factors. IHC plays a limited, even though important, role in the diagnosis of salivary gland tumors, but is often useful to support the histological assessment. However, unfortunately few tumor type-specific markers are still currently available. For these reasons, IHC should be considered a method that can be used to assist the final diagnosis, and its results themselves do not directly indicate a definitive diagnosis.

Comparison of Kupffer-phase Sonazoid-enhanced sonography and hepatobiliary-phase gadoxetic acid-enhanced magnetic resonance imaging of hepatocellular carcinoma and correlation with histologic grading.

To determine the relative wash‐out of hepatocellular carcinomas and dysplastic nodules using Kupffer‐phase sonography with Sonazoid (Daiichi‐Sankyo, Tokyo, Japan) enhancement and hepatobiliary‐phase gadoxetic acid‐enhanced magnetic resonance imaging (MRI) in the evaluation of the histopathologic grades of individual nodules.

Preferential expression of potential markers for cancer stem cells in large cell neuroendocrine carcinoma of the lung. An FFPE proteomic study

BackgroundLarge cell neuroendocrine carcinoma (LCNEC) of the lung, a subtype of large cell carcinoma (LCC), is characterized by neuroendocrine differentiation that small cell lung carcinoma (SCLC) shares. Pre-therapeutic histological distinction between LCNEC and SCLC has so far been problematic, leading to adverse clinical outcome. We started a project establishing protein targets characteristic of LCNEC with a proteomic method using formalin fixed paraffin-embedded (FFPE) tissues, which will help make diagnosis convincing.MethodsCancer cells were collected by laser microdissection from cancer foci in FFPE tissues of LCNEC (n = 4), SCLC (n = 5), and LCC (n = 5) with definite histological diagnosis. Proteins were extracted from the harvested sections, trypsin-digested, and subjected to HPLC/mass spectrometry. Proteins identified by database search were semi-quantified by spectral counting and statistically sorted by pair-wise G-statistics. The results were immunohistochemically verified using a total of 10 cases for each group to confirm proteomic results.ResultsA total of 1981 proteins identified from the three cancer groups were subjected to pair-wise G-test under p < 0.05 and specificity of a proteins expression to LCNEC was checked using a 3D plot with the coordinates comprising G-statistic values for every two group comparisons. We identified four protein candidates preferentially expressed in LCNEC compared with SCLC with convincingly low p-values: aldehyde dehydrogenase 1 family member A1 (AL1A1) (p = 6.1 × 10-4), aldo-keto reductase family 1 members C1 (AK1C1) (p = 9.6x10-10) and C3 (AK1C3) (p = 3.9x10-10) and CD44 antigen (p = 0.021). These p-values were confirmed by non-parametric exact inference tests. Interestingly, all these candidates would belong to cancer stem cell markers. Immunohistochmistry supported proteomic results.ConclusionsThese results suggest that candidate biomarkers of LCNEC were related to cancer stem cells and this proteomic approach via FFPE samples was effective to detect them.

Quantification in molecular ultrasound imaging: a comparative study in mice between healthy liver and a human hepatocellular carcinoma xenograft.

The purpose of this study was to quantitatively assess the contrast kinetics of vascular endothelial growth factor receptor 2 (VEGFR2)‐targeted microbubbles (BR55; Bracco Suisse, Geneva, Switzerland) compared to clinically used microbubbles (SonoVue; Bracco SpA, Milan, Italy) in both normal liver and human hepatocellular carcinoma xenograft tumors in mice.

Assessment of various types of US findings after irreversible electroporation in porcine liver: comparison with radiofrequency ablation.

PURPOSE To assess various ultrasound (US) findings, including B-mode, shear-wave elastography (SWE), and contrast-enhanced US, in accurately assessing ablation margins after irreversible electroporation (IRE) based on radiologic-pathologic correlation, and to compare these findings between IRE and radiofrequency (RF) ablation. MATERIALS AND METHODS IRE (n = 9) and RF ablation (n = 3) were performed in vivo in three pig livers. Each ablation zone was imaged by each method immediately after the procedure and 90 minutes later. Ablation zones were evaluated based on gross pathologic and histopathologic findings in samples from animals euthanized 2 hours after the last ablation. The characteristics and dimensions of the histologic ablation zones were qualitatively and quantitatively compared against each US finding. RESULTS In B-mode US at 90 minutes after IRE, the ablation zones appeared as hyperechoic areas with a peripheral hyperechoic rim, showing excellent correlation (r(2) = 0.905, P < .0001) with gross pathologic findings. SWE showed that tissue stiffness in the IRE ablation zones increased over time. Contrast-enhanced US depicted the IRE ablation zones as hypovascular areas in the portal phase, and showed the highest correlation (r(2) = 0.923, P < .0001) with gross pathologic findings. The RF ablation zones were clearly visualized by B-mode US. SWE showed that tissue stiffness after RF ablation was higher than after IRE. Contrast-enhanced US depicted the RF ablation zones as avascular areas. CONCLUSIONS IRE and RF ablation zones can be most accurately predicted by portal-phase contrast-enhanced US measurements obtained immediately after ablation.

Relationship Between the Liver Tissue Shear Modulus and Histopathologic Findings Analyzed by Intraoperative Shear Wave Elastography and Digital Microscopically Assisted Morphometry in Patients With Hepatocellular Carcinoma

Shear wave elastography is a novel noninvasive method for assessing liver fibrosis by measuring liver stiffness. This study was conducted to evaluate how pathologic changes could have an impact on measured elasticity values in both resected hepatocellular carcinomas and adjacent liver tissue.

Radiologic-pathologic correlation of three-dimensional shear-wave elastographic findings in assessing the liver ablation volume after radiofrequency ablation

AIM To evaluate the usefulness of three-dimensional (3D) shear-wave elastography (SWE) in assessing the liver ablation volume after radiofrequency (RF) ablation. METHODS RF ablation was performed in vivo in 10 rat livers using a 15-gauge expandable RF needle. 3D SWE as well as B-mode ultrasound (US) were performed 15 min after ablation. The acquired 3D volume data were rendered as multislice images (interslice distance: 1.10 mm), and the estimated ablation volumes were calculated. The 3D SWE findings were compared against digitized photographs of gross pathological and histopathological specimens of the livers obtained in the same sectional planes as the 3D SWE multislice images. The ablation volumes were also estimated by gross pathological examination of the livers, and the results were then compared with those obtained by 3D SWE. RESULTS In B-mode US images, the ablation zone appeared as a hypoechoic area with a peripheral hyperechoic rim; however, the findings were too indistinct to be useful for estimating the ablation area. 3D SWE depicted the ablation area and volume more clearly. In the images showing the largest ablation area, the mean kPa values of the peripheral rim, central zone, and non-ablated zone were 13.1 ± 1.5 kPa, 59.1 ± 21.9 kPa, and 4.3 ± 0.8 kPa, respectively. The ablation volumes depicted by 3D SWE correlated well with those estimated from gross pathological examination (r (2) = 0.9305, P = 0.00001). The congestion and diapedesis of red blood cells observed in histopathological examination were greater in the peripheral rim of the ablation zone than in the central zone. CONCLUSION 3D SWE outperforms B-mode US in delineating ablated areas in the liver and is therefore more reliable for spatially delineating thermal lesions created by RF ablation.

Focal nodular hyperplasia-like lesion of the liver with focal adenoma features associated with idiopathic portal hypertension

Great progress has been made in the diagnosis of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) in the last few years due to the use of molecular criteria. This has allowed us to identify a new type of hepatic nodule. In this case report, we present a male patient with a hepatic nodule associated with idiopathic portal hypertension (IPH) pathologically exhibiting not only the morphological features of FNH, such as ductular reactions, dilated sinusoids, major vascular abnormalities and an immunohistochemical “map‐like” pattern of glutamine synthetase (GS), but also the immunohistological features of focal HCA, such as strong expression of serum amyloid A and C‐reactive protein and weak expression of GS. As the final diagnosis, the nodule was identified as an FNH‐like lesion with focal inflammatory hepatocellular adenoma.

Two cases of sclerosing angiomatoid nodular transformation of the spleen with gradual growth: usefulness of diffusion-weighted imaging

Sclerosing angiomatoid nodular transformation (SANT) is a recently recognized and rare, nonneoplastic lesion of the spleen. Some papers have reported an increased SANT diameter during the follow-up period. We present two cases of SANT whose size increased during the follow-up period. Diffusion-weighted magnetic resonance imaging (DWI) findings correlated well with the pathological findings of SANT, the multinodular high-intensity area as the angiomatoid nodules and the peripheral low-intensity area as fibrous tissues. Therefore, DWI may be a useful imaging tool.

Retrograde Lymphatic Spread of Esophageal Cancer: A Case Report

AbstractThe concept of the retrograde lymphatic spread of cancer cells appears to account for a subset of the essential mechanisms of cancer metastasis in various organs. However, no adequate data currently exist to illustrate the pathology of the retrograde lymphatic metastasis of cancer cells in human bodies. To shed light on this phenomenon, we report a case of a 63-year-old Japanese man who underwent an esophagectomy and lymph node dissection for early-stage esophageal cancer.The patients clinical information was evaluated by board-certified surgeons and internists. Surgically excised materials were histopathologically evaluated by attending pathologists.Postoperative pathological examination revealed that the patients tumor was a well-differentiated squamous cell carcinoma with negative surgical margins (T1N0M0, stage I). Apart from the primary lesion, a single lymphatic vessel invasion was found between the lamina propria and lamina muscularis of the esophagus where intralymphatic cancer cells had spread against the direction of backflow prevention valves and skipped beyond these valves without destroying them.The present case demonstrated that the retrograde lymphatic spread of cancer cells can occur in valve-equipped lymphatic vessels. Our study may not only provide a scientific basis for the concept of retrograde lymphatic metastasis but also explain a portion of the complexities associated with the lymphogenous metastasis of esophageal cancer.