Computer-aided classification of hepatocellular ballooning in liver biopsies from patients with NASH using persistent homology.

BACKGROUND AND OBJECTIVE: Hepatocellular ballooning is an important histological parameter in the diagnosis of nonalcoholic steatohepatitis (NASH), and it is considered to be a morphological pattern that indicates the severity and the progression to cirrhosis and liver-related deaths. There remains uncertainty about the pathological criteria for evaluating the spectrum of non-alcoholic fatty liver disease (NAFLD) in liver biopsies. We introduce persistence images as novel mathematical descriptors for the classification of ballooning degeneration in the pathological diagnosis. METHODS: We implemented and tested a topological data analysis methodology combined with linear machine learning techniques and applied this to the classification of tissue images into NAFLD subtypes using Matteoni classification in liver biopsies. RESULTS: Digital images of hematoxylin- and eosin-stained specimens with a pathologist's visual assessment were obtained from 79 patients who were clinically diagnosed with NAFLD. We obtained accuracy rates of more than 90% for the classification between NASH and non-NASH NAFLD groups. The highest area under the curve from the receiver operating characteristic analysis was 0.946 for the classification of NASH and NAFL2 (type 2 of Matteoni classification), when both 0- and 1-dimensional persistence images were used. CONCLUSIONS: Our methodology using persistent homology provides quantitative measurements of the topological features in liver biopsies of NAFLD groups with considerable accuracy.

Persistent homology index as a robust quantitative measure of immunohistochemical scoring.

Immunohistochemical data (IHC) plays an important role in clinical practice, and is typically gathered in a semi-quantitative fashion that relies on some degree of visual scoring. However, visual scoring by a pathologist is inherently subjective and manifests both intra-observer and inter-observer variability. In this study, we introduce a novel computer-aided quantification methodology for immunohistochemical scoring that uses the algebraic concept of persistent homology. Using 8 bit grayscale image data derived from 90 specimens of invasive ductal carcinoma of the breast, stained for the replicative marker Ki-67, we computed homology classes. These were then compared to nuclear grades and the Ki-67 labeling indices obtained by visual scoring. Three metrics for IHC staining were newly defined: Persistent Homology Index (PHI), center coordinates of positive and negative groups, and the sum of squares within groups (WSS). This study demonstrates that PHI, a novel index for immunohistochemical labeling using persistent homology, can produce highly similar data to that generated by a pathologist using visual evaluation. The potential benefits associated with our novel technology include both improved quantification and reproducibility. Since our method reflects cellularity and nuclear atypia, it carries a greater quantity of biologic data compared to conventional evaluation using Ki-67.

A case of extrahepatic growth-type hepatocellular carcinoma presenting with bleeding from colonic metastasis.

A 60-year-old woman visited our hospital due to hematochezia. Colonoscopy revealed a 50-mm-diameter submucosal tumor with ulceration of the left side of the transverse colon, and magnetic resonance imaging (MRI) demonstrated the presence of small hepatic nodules. Submucosal tumor of the colon with liver metastasis was therefore diagnosed. To prevent tumor bleeding, we performed partial transverse colectomy. The histopathological diagnosis was moderately differentiated hepatocellular carcinoma presenting as a submucosal tumor with a high frequency of vascular invasion. Computed tomography (CT) angiography revealed a 40-mm-diameter confluent multinodular-type hepatocellular carcinoma with outward spread from segment II and multiple intrahepatic metastases. Our final diagnosis was hepatocellular carcinoma with hematogenous colon metastasis.

Homology-based method for detecting regions of interest in colonic digital images.

BACKGROUND: A region of interest (ROI) is a part of tissue that contains important information for diagnosis. To use many image analysis methods efficiently, a technique that would allow for ROI identification is required. For the colon, ROIs are characterized by areas of stronger color intensity of hematoxylin. Since malignant tumors grow in the innermost layer, most ROIs will be located in the colonic mucosa and will be an accumulation of tumor cells and/or integrated cells with distorted architecture. METHODS: Using homology theory, our group proposed a method to estimate the contact degree of elements in a unit area of tissue. Homology is a concept that is used in many branches of algebra and topology, and it can quantify the contact degree. Due to the lack of contact inhibition of cancer cells, an area with unusual contact degree is expected to be a potential ROI. RESULTS: The current work verifies the accuracy of this method against the results of pathological diagnosis, based on 1825 colonic images provided by the Osaka Medical Center for Cancer and Cardiovascular Diseases. Although we have many false positives and there is a possibility of missing undifferentiated types of cancer, this system is very effective for detecting ROIs. CONCLUSIONS: The mathematical system proposed by our group successfully detects ROIs and is a potentially useful tool for differentiating tumor areas in microscopic examination very quickly. Because we use only the information from low-power field images, there is room for further improvement. This system could be used to screen for not only colon cancer but other cancers as well. More sophisticated and more efficient automated pathological diagnosis systems can be developed by integrating various techniques available today. VIRTUAL SLIDE: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7129390011429407 .

[A case of adenoendocrine cell carcinoma on the ampulla of Vater].

The occurrence of an adenoendocrine cell carcinoma on the ampulla of Vater is rare, especially when the component of adenocarcinoma is not located on the mucosa of the ampulla. A 76-year-old man was referred to our hospital for further investigation of a mass lesion on the ampulla. EGD revealed SMT like mass lesion on the ampulla. Endoscopic ultrasonography showed an ampullary hypoechoic mass. We performed pylorus-preserving pancreatoduodenectomy on the basis of the diagnosis of poorly differentiated adenocarcinoma of the ampulla of Vater. Postoperative pathological examinations revealed two different components of the tumor;malignant endocrine cells, and adenocarcinoma. The component of adenocarcinoma was located on the Ap lesion. We deducted that the adenocarcinoma appeared on the epithelium of Ap, then grew and spread into the direction of duodenum lumen, degenerating to endocrine cells.

Primary mediastinal liposarcoma, with 6 years of follow-up to autopsy, revealed histopathological features of primary and metastatic lesions.

Primary mediastinal liposarcoma was observed in a 73-year-old man. Because of tight adhesions to adjacent tissues, neither complete resection nor surgical debulking of the tumor was possible. A T-tube was inserted into the patient's trachea for severe dyspnea, and he was treated with radiotherapy and an oral peroxisome proliferator-activated receptor-gamma agonist. The patient died 6 years after the initial diagnosis. Autopsy revealed liposarcoma composed of 3 subtypes in the primary tumor: well-differentiated, dedifferentiated, and round cell components. Round cell and dedifferentiated liposarcomas were predominantly observed in the metastatic nodules.

Sudden death of a patient with pandemic influenza (A/H1N1pdm) virus infection by acute respiratory distress syndrome.

We describe an autopsy case of a patient with pandemic influenza (A/H1N1pdm) virus infection in Japan, who developed rapidly progressive viral pneumonia exhibiting diffuse alveolar damage. A 41-year-old female visited our hospital with a fever of 38.7C. She was a public health nurse with no underlying disease and had had contact with a group of elementary school students who had been infected with the influenza (A/H1N1pdm) virus 1 week earlier. She was prescribed oseltamivir and returned to the hotel where she was staying alone. The next day, she was found dead in her hotel room. At autopsy, both lungs were voluminous and microscopic examination revealed acute-stage, severe diffuse alveolar damage with remarkable mononuclear cell infiltration and hyaline membrane formation in the lungs. CD8-positive T lymphocytes were dominantly observed. Immunohistochemically, influenza A viral protein was confirmed in the damaged type II pneumocytes and also in the infiltrated macrophages. Real-time RT-PCR analysis of both pre- and post-mortem pharyngeal swabs confirmed a novel influenza (A/H1N1pdm) virus infection. This is the second autopsy case of influenza (A/H1N1pdm) virus infection in Japan, and the findings indicated that the patient died due to an exceptionally rapid progression of viral pneumonia. This case indicates that patients with influenza (A/H1N1pdm) virus infection should be carefully monitor for acute respiratory distress syndrome.

CNS lymphomatoid granulomatosis with lymph node and bone marrow involvements.

Lymphomatoid granulomatosis (LYG) in the CNS is an uncommon lymphoproliferative disease with characteristic angiocentric lymphoreticular proliferative and granulomatous lesions exhibiting low-grade malignant potential. Here we report a rare case of CNS-LYG, which disseminated to the lymph node and bone marrow. A 50-year-old man was diagnosed with CNS-LYG based on brain biopsy showing perivascular infiltration of CD3-positive small T-lymphocytes without overt nuclear atypism. Eight months after the initial neurological symptoms, inguinal lymph node swelling was found and histopathologically diagnosed as peripheral T-cell lymphoma. TCRgamma-gene rearrangement study using both paraffin-embedded specimens of brain and inguinal lymph node demonstrated an identical clonal band. Considering the clinical course, we concluded lymph node involvement of CNS-LYG, suggesting the malignant potential of CNS-LYG.

Chromophobe renal cell carcinoma with osteosarcoma-like differentiation.

Sarcomatoid differentiation in renal cell carcinoma is thought to be the result of the dedifferentiation of the parent tumor, and it can be found in the chromophobe renal cell carcinoma just as other subtypes. We report a case of chromophobe renal cell carcinoma, which showed osteosarcoma-like differentiation. This is the first known case ever to be clearly identified as such. The patient was a 74-year-old man, and the CT scan revealed a huge retroperitoneal mass, which protruded from the lower half of the kidney and directly invaded the colon. Intraabdominal dissemination and metastases to the liver and lungs were also found. The resected tumor histologically showed sarcoma-like spindle cell proliferation and partly produced massive osteoid, which simulated the osteosarcoma. In addition, a typical histology of chromophobe renal cell carcinoma was found in part of the tumor. Immunohistochemically, spindle cells were reactive for epithelial membrane antigen, cytokeratin, and vimentin. The cell nests that were labeled by epithelial membrane antigen and cytokeratin were also found in the osteosarcoma-like area. We think that these phenomena were the result of "dedifferentiation" and metaplasia of the chromophobe renal cell carcinoma.