Plasma Aldo-Keto Reductase Family 1 Member B10 as a Biomarker Performs Well in the Diagnosis of Nonalcoholic Steatohepatitis and Fibrosis.

We found several blood biomarkers through computational secretome analyses, including aldo-keto reductase family 1 member B10 (AKR1B10), which reflected the progression of nonalcoholic fatty liver disease (NAFLD). After confirming that hepatic AKR1B10 reflected the progression of NAFLD in a subgroup with NAFLD, we evaluated the diagnostic accuracy of plasma AKR1B10 and other biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) and fibrosis in replication cohort. We enrolled healthy control subjects and patients with biopsy-proven NAFLD (n = 102) and evaluated the performance of various diagnostic markers. Plasma AKR1B10 performed well in the diagnosis of NASH with an area under the receiver operating characteristic (AUROC) curve of 0.834 and a cutoff value of 1078.2 pg/mL, as well as advanced fibrosis (AUROC curve value of 0.914 and cutoff level 1078.2 pg/mL), with further improvement in combination with C3. When we monitored a subgroup of obese patients who underwent bariatric surgery (n = 35), plasma AKR1B10 decreased dramatically, and 40.0% of patients with NASH at baseline showed a decrease in plasma AKR1B10 levels to below the cutoff level after the surgery. In an independent validation study, we proved that plasma AKR1B10 was a specific biomarker of NAFLD progression across varying degrees of renal dysfunction. Despite perfect correlation between plasma and serum levels of AKR1B10 in paired sample analysis, its serum level was 1.4-fold higher than that in plasma. Plasma AKR1B10 alone and in combination with C3 could be a useful noninvasive biomarker for the diagnosis of NASH and hepatic fibrosis.

The efficacy of real-time colour Doppler flow imaging on endoscopic ultrasonography for differential diagnosis between neoplastic and non-neoplastic gallbladder polyps.

OBJECTIVES: We evaluated the usefulness of real-time colour Doppler flow (CDF) endoscopic ultrasonography (EUS) for differentiating neoplastic gallbladder (GB) polyps from non-neoplastic polyps. METHODS: Between August 2014 and December 2016, a total of 233 patients with GB polyps who underwent real-time CDF-EUS were consecutively enrolled in this prospective study. CDF imaging was subjectively categorized for each patient as: strong CDF pattern, weak CDF pattern and no CDF pattern. RESULTS: Of the 233 patients, 115 underwent surgical resection. Of these, there were 90 cases of non-neoplastic GB polyps and 23 cases of neoplastic GB polyps. In a multivariate analysis, a strong CDF pattern was the most significant predictive factor for neoplastic polyps; sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 52.2 %, 79.4 %, 38.7 %, 86.9 % and 73.9 %, respectively. Solitary polyp and polyp size were associated with an increased risk of neoplasm. CONCLUSIONS: The presence of a strong CDF pattern as well as solitary and larger polyps on EUS may be predictive of neoplastic GB polyps. As real-time CDF-EUS poses no danger to the patient and requires no additional equipment, it is likely to become a supplemental tool for the differential diagnosis of GB polyps. KEY POINTS: • Differential diagnosis between neoplastic polyps and non-neoplastic polyps of GB is limited. • The use of real-time CDF-EUS was convenient, with high agreement between operators. • The real-time CDF-EUS is helpful in differential diagnosis of GB polyps.

Clinicopathologic Similarities of the Main and Minor Lesions of Synchronous Multiple Early Gastric Cancer.

The detection rate of early gastric cancer (EGC) is increasing due to improvements in diagnostic methods, but synchronous multiple EGC (SMEGC) remains a major problem. Therefore, we investigated the characteristics of and the correlation between the main and minor lesions of SMEGC. We retrospectively reviewed the medical records of patients with EGC between April 2008 and May 2013. The main lesion was defined as the one with the greatest invasion depth. If lesions had the same invasion depth, the tumor diameter was used to define the main lesion. Of 963 patients who had treatment for EGC, 37 patients with SMEGC were analyzed. The main and minor lesions showed a significant positive correlation of size (r = 0.533, P = 0.001). The main and minor lesions of SMEGC showed the same vertical and horizontal locations at 70.3% and 64.9%, respectively (P = 0.002 and P = 0.002). Macroscopic types were identical in 67.6% (P < 0.001), and 32.4% had identical macroscopic type and location. The main and minor lesions had identical characteristics of invasion depth, presence of lymphovascular invasion (LVI), and differentiation in 78.4%, 83.8%, and 83.8%, respectively. Differentiation, LVI, and invasion depth (microscopic characteristics) were simultaneously the same in 62.2%. The location, macroscopic type, and 3 microscopic characteristics were matched in 27%. The main and minor lesions of SMEGC have similar clinicopathologic characteristics. Therefore, the possibility of SMEGC should not be neglected in cases of EGC, considering an understanding of the characteristics and association of lesions.

A thrombotic primary venous aneurysm of an upper extremity causing pulmonary emboli after it was squeezed.

A 27-year-old Korean male complained of chest pain and dyspnea that began after he had squeezed a mass on the medial side of his right upper arm. Computed tomography angiography and venous Doppler ultrasonography revealed a right basilic vein aneurysm with an organized thrombosis causing pulmonary emboli. After 1 month of anticoagulation, the aneurysm was ligated and resected. During the operation, multiple venous aneurysms filled with organized thrombi were observed. This is the first reported case of a thrombotic primary venous aneurysm of an upper extremity causing pulmonary emboli after it was squeezed.

Squash Cytology of a Dural-Based High-Grade Chondrosarcoma May Mimic That of Glioblastoma in the Central Nervous System.

BACKGROUND: Intracranial chondrosarcoma is rare, and most cases occur in the skull base. Intradural chondrosarcoma is even rarer. CASE: Here, we describe a case of dural chondrosarcoma with a radiation history for nasopharyngeal carcinoma and a radical prostatectomy for prostatic cancer 15 and 8 years earlier, respectively. A 67-year-old man presented with a 3-week memory disturbance and dysarthria. Computed tomography and magnetic resonance images of the brain revealed a dural-based mass in the left temporal area. Under the impression of a glioblastoma, a resection and an intraoperative squash cytology were done. A necrotic dirty background as well as bluish-to-pinkish myxoid stroma were characteristic; the nuclei of highly pleomorphic tumor cells were hyperchromatic to vesicular with an occasional ground-glass appearance. The cytoplasm was of an eosinophilic hyalinized condensed morphology with an occasional granular appearance. Histologically, the lobulated mass was composed of hypercellular lobules of well-differentiated chondrocytes intermixed with anaplastic pleomorphic cells and diagnosed as a conventional grade III chondrosarcoma. These cells were immunoreactive for D2-40, S-100 protein and vimentin. Brain invasion was also found. CONCLUSION: Albeit rare, dural-based chondrosarcomas should be considered in the differential diagnosis for meningeal tumors, especially in the case of previous radiation therapy.

A Case of Pneumonia Caused by Pneumocystis jirovecii Resistant to Trimethoprim-Sulfamethoxazole.

A 50-year-old male visited the outpatient clinic and complained of fever, poor oral intake, and weight loss. A chest X-ray demonstrated streaky and fibrotic lesions in both lungs, and chest CT revealed multifocal peribronchial patchy ground-glass opacities with septated cystic lesions in both lungs. Cell counts in the bronchoalveolar lavage fluid revealed lymphocyte-dominant leukocytosis, and further analysis of lymphocyte subsets showed a predominance of cytotoxic T cells and few T helper cells. Video-assisted wedge resection of the left upper lobe was performed, and the histologic examination was indicative of a Pneumocystis jirovecii infection. Trimethoprim-sulfamethoxazole (TMP-SMX) was orally administered for 3 weeks; however, the patient complained of cough, and the pneumonia was aggravated in the follow-up chest X-ray and chest CT. Molecular studies demonstrated mutations at codons 55 and 57 of the dihydropteroate synthase (DHPS) gene, which is associated with the resistance to TMP-SMX. Clindamycin-primaquine was subsequently administered for 3 weeks replacing the TMP-SMX. A follow-up chest X-ray showed that the pneumonia was resolving, and the cough was also alleviated. A positive result of HIV immunoassay and elevated titer of HCV RNA indicated HIV infection as an underlying condition. This case highlights the importance of careful monitoring of patients with P. jirovecii pneumonia (PCP) during the course of treatment, and the molecular study of DHPS mutations. Additionally, altering the anti-PCP drug utilized as treatment must be considered when infection with drug-resistant P. jirovecii is suspected. To the best of our knowledge, this is the first case of TMP-SMX-resistant PCP described in Korea.

Intraabdominal abscess caused by actinomycosis in a patient with mesenteric fibromatosis of the small intestine: report of a case.

A 38-year-old man presented to our Emergency Department with acute severe abdominal pain; 3 days after, a mesenteric mass had been detected by abdomino-pelvic computed tomography. Emergency laparotomy revealed a mesenteric mass with focal surface rupture. Microscopically, the mesenteric mass was composed of fibroblast-like spindle cells with intervening marked collagen deposits. These spindle cells were positive for nuclear ß-catenin and negative for CD34, c-kit, smooth muscle actin, and S-100 protein. We diagnosed the mesenteric lesion as deep fibromatosis, consistent with mesenteric fibromatosis (MF). Serial sections of the ruptured portion showed abscess formation with a peripheral radiating pattern of microcolonies, proven to be actinomycosis by Grocott's methenamine silver stain and gram staining. One glandular fragment was found in the adhered muscle layers and a foreign body reaction was seen within the abscess cavity. We speculate that MF involved the serosal adhesions between the adjacent bowel walls and the subsequent fibrous pulling might have created the connection between the bowel lumen and the bowel wall. This disrupted barrier led to the Actinomyces infection. To our knowledge, this is the first report of sporadic MF leading to the formation of an abscess cavity with rupture and actinomycosis.

Crush cytologic findings of a cerebral granular cell astrocytoma.

BACKGROUND: Granular cell astrocytoma (GCA) is a rare variant of astrocytoma, characterized by an aggressive prognosis compared to conventional astrocytomas of the same World Health Organization grade. Intraoperative smears provide useful clues in diagnosing neuropathology, especially in rarely encountered central nervous system tumors. CASE: The patient was a 53-year-old man who presented with a huge mass at the left temporal lobe with peritumoral edema on MRI. The crush smears revealed singly-scattered, large eosinophilic cells with eccentrically located nuclei as well as plump, finely-granular cytoplasm with distinct borders. Mild cellular atypia and absence of mitotic activity were noted. These cells were admixed with small mature lymphoid cells. Histology showed scattered large granular cells which were positive for glial fibrillary acidic protein. CONCLUSION: The most helpful imprint cytologic findings of GCA were as follows: (1) large cells containing eosinophilic granular cytoplasm rather than the foamy or bubbly cytoplasm associated with macrophages or renal cell carcinomas; (2) distinct granular cell borders in contrast to the ruffled membrane of macrophages, and (3) markedly large-sized granular cells, ranging from 60 to 100 µm in diameter.

A case of ossified laryngeal cartilage mimicking a subglottic mass.

A previously healthy 54-year-old man complained of progressive voice changes. A firm subglottic polypoid mass was located at the right posterior site, as seen on fiberoptic laryngoscopy, with a distinctly narrowed subglottic space being seen on neck computed tomography, and there were multiple opacities from the cricoid cartilage to the tracheal rings. Resection was done under general anesthesia. The mass-like elevated lesion showed enchondral ossification of the laryngeal cartilage just beneath the squamous metaplastic surface epithelium. The vocal cord mobility was normal. Compared with the computed tomography and the laryngoscopic examination, the polypoid mass-like elevation corresponded to a ossified vocal process of the right arytenoid cartilage. To date, clinically symptomatic ossification of the laryngeal cartilages has presented with foreign body-like impaction. The present case is a rare case of ossification of the laryngeal cartilage that masqueraded as a subglottic polypoid mass. The ossification of laryngeal cartilage is part of the normal aging process, but a tumor-like mass at the airway related with voice changes, like was seen in the present case, is rare. Albeit rare, clinicians and radiologists should be aware that this heterotopic ossification may mimic a polypoid mass-like presentation as well as the accompanying symptoms.

MRI Findings of Renal Myxoma: A Case Report and Literature Review.

Renal myxomas are very rare benign tumors. To date, a few cases have been reported in English literature, mostly in pathology and urology journals. Thus, there are few reports on the radiological findings associated with renal myxomas. We report on the imaging findings in a case of renal myxoma in a 62-year-old male. MRI demonstrated a well-defined mass in the left renal sinus, with intermediate high signal intensity on T2-weighted images and low signal intensity on T1-weighted images. The tumor showed gradual enhancement on contrast-enhanced T1-weighted images.

Marginal zone B-cell lymphoma of MALT in small intestine associated with amyloidosis: a rare association.

A 62-yr-old man presented with a 5-yr history of intermittent abdominal distention and pain. These symptoms persisted for several months and subsided without treatment. A diagnosis of suspected small bowel lymphoma was made based on plain radiograph and computerized tomogram findings, and he was referred to our institution for further evaluation. Segmental resection of the small intestine was performed and the diagnosis of marginal zone B-cell lymphoma associated with amyloidosis was made. This is the first case of marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) in the small intestine associated with amyloidosis in Korea.

Magnetic Resonance-Based Assessments Better Capture Pathophysiologic Profiles and Progression in Nonalcoholic Fatty Liver Disease.

BACKGROUND: Several noninvasive tools are available for the assessment of nonalcoholic fatty liver disease (NAFLD) including clinical and blood biomarkers, transient elastography (TE), and magnetic resonance imaging (MRI) techniques, such as proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE). In the present study, we aimed to evaluate whether magnetic resonance (MR)-based examinations better discriminate the pathophysiologic features and fibrosis progression in NAFLD than other noninvasive methods. METHODS: A total of 133 subjects (31 healthy volunteers and 102 patients with NAFLD) were subjected to clinical and noninvasive NAFLD evaluation, with additional liver biopsy in some patients (n=54). RESULTS: MRI-PDFF correlated far better with hepatic fat measured by MR spectroscopy (r=0.978, P<0.001) than with the TE controlled attenuation parameter (CAP) (r=0.727, P<0.001). In addition, MRI-PDFF showed stronger correlations with various pathophysiologic parameters for cellular injury, glucose and lipid metabolism, and inflammation, than the TE-CAP. The MRI-PDFF and TE-CAP cutoff levels associated with abnormal elevation of serum alanine aminotransferase were 9.9% and 270 dB/m, respectively. The MRE liver stiffness measurement (LSM) showed stronger correlations with liver enzymes, platelets, complement component 3, several clinical fibrosis scores, and the enhanced liver fibrosis (ELF) score than the TE-LSM. In an analysis of only biopsied patients, MRE performed better in discriminating advanced fibrosis with a cutoff value of 3.9 kPa than the TE (cutoff 8.1 kPa) and ELF test (cutoff 9.2 kPa). CONCLUSION: Our results suggest that MRI-based assessment of NAFLD is the best non-invasive tool that captures the histologic, pathophysiologic and metabolic features of the disease.

Ovarian malignant melanoma without evidence of teratoma.

A 46-year-old woman with ovarian malignant melanoma had advanced intraperitoneal metastasis, retroperitoneal and inguinal lymph node metastases. Extensive debulking surgery was performed and chemotherapy was given. Microscopically, no evidence of other accompanying tumor, such as teratoma was noted. Detailed examination of the patient failed to identify any evidence of another primary melanoma site. It is assumed that spontaneous regression of the primary lesion occurred. Despite the surgery and chemotherapy, the patient died within 2 months of diagnosis. Considering this case, it is assumed that the combination of surgical debulking and chemotherapy are not always beneficial in ovarian malignant melanoma and the prognosis of ovarian malignant melanoma is very poor.

Primary carcinoid tumor in the external auditory canal.

A 39-year-old man visited the department of otolaryngology due to an ongoing hearing disturbance that had lasted for 1 year. Temporal bone computed tomography revealed soft tissue density nearly obliterating the left external auditory canal (EAC). The mass was composed of sheets of round tumor cells containing moderate amounts of fine granular cytoplasm and salt and pepper chromatin. Neither mitosis nor necrosis was found. The Ki-67 proliferation index was less than 2%. Cells were positive for CD56 and synaptophysin but negative for chromogranin, cytokeratin (CK) 20, and CK7. Based on these findings, the tumor was diagnosed as a carcinoid tumor, well differentiated neuroendocrine carcinoma, grade 1 (G1) according to current World Health Organization (WHO) classification of head and neck tumors; and a neuroendocrine tumor, G1 according to neuroendocrine neoplasm (NEN)-2018 WHO standard classification. He remained free of local recurrence and metastasis after 20 months of follow up. To date, only six cases of primary NENs in the EAC have been reported. Metastatic tumor should be included in the differential diagnoses. Because of its rarity, the prognosis and treatment have not yet been clarified.

Human Immunodeficiency Virus-Associated Gastrointestinal Kaposi's Sarcoma: A Case Report.

Kaposi's sarcoma (KS) is a multicentric human immunodeficiency virus-associated neoplasm characterized by multiple vascular nodules in the skin, mucous membranes, and viscera. Gastrointestinal acquired immunodeficiency syndrome (AIDS)-related KS is the most common visceral involvement reported in disseminated disease. Here, we present the findings of a rare case of KS involving multiple organs with abdominal pain and active bleeding in the colon. Multiple intraluminal lesions were found in the terminal ileum, sigmoid colon, and rectum by ileocolonoscopy, and in the jejunum and ileum by fluoroscopy. Abdominopelvic CT revealed multiple enhanced flat lesions in the ileum and enlarged lymph nodes. The diagnosis was confirmed by histopathology, and antiretroviral therapy was initiated as the treatment of choice for KS. Owing to the increasing number of AIDS patients, it is essential for radiologists and clinicians to be aware of the imaging characteristics of KS to protect physicians from indiscriminate exposure to AIDS.

Contribution of cytologic examination to diagnosis of poorly differentiated thyroid carcinoma.

BACKGROUND: The cytologic diagnosis of poorly differentiated thyroid carcinoma (PDTC) is difficult because it lacks salient cytologic findings and shares cytologic features with more commonly encountered neoplasms. Due to diverse cytologic findings and paucicellularity of PDTC, standardization of cytologic diagnostic criteria is limited. The purpose of this study is to investigate and recognize diverse thyroid findings of fine needle aspiration (FNA) cytology and frozen smear cytology in diagnosis of this rare but aggressive carcinoma. METHODS: The present study included six cases of FNA cytology and frozen smears of histologically diagnosed PDTCs. RESULTS: PDTC showed cytologic overlap with well-differentiated thyroid carcinomas (WDTCs). Five of six cases showed dedifferentiation arising from well differentiated thyroid carcinomas. Only one de novo PDTC showed highly cellular smears composed of discohesive small cells, high nuclear/cytoplasmic (N/C) ratio, prominent micronucleoli, and irregular nuclei. Retrospectively reviewed, these findings are highly suspicious for PDTC. Cytologic findings of nuclear atypia, pleomorphism, and irregularity were frequently found, whereas scattered small cells were seen only in the de novo case. CONCLUSIONS: Heterogeneous cytologic findings of PDTCs are shared with those of WDTCs and contribute to difficult preoperative cytologic diagnoses. Most PDTCs show dedifferentiation from WDTCs. Albeit rare, de novo PDTC should be considered with cytology showing discohesive small cells with high N/C ratio. This will enable precise diagnosis and prompt treatment of this aggressive malignancy.

Comparison of papanicolaou smear and human papillomavirus (HPV) test as cervical screening tools: can we rely on HPV test alone as a screening method? An 11-year retrospective experience at a single institution.

BACKGROUND: The decrease in incidence of cervical dysplasia and carcinoma has not been as dramatic as expected with the development of improved research tools and test methods. The human papillomavirus (HPV) test alone has been suggested for screening in some countries. The National Cancer Screening Project in Korea has applied Papanicolaou smears (Pap smears) as the screening method for cervical dysplasia and carcinoma. We evaluated the value of Pap smear and HPV testing as diagnostic screening tools in a single institution. METHODS: Patients co-tested with HPV test and Pap smear simultaneously or within one month of each other were included in this study. Patients with only punch biopsy results were excluded because of sampling errors. A total of 999 cases were included, and the collected reports encompassed results of smear cytology, HPV subtypes, and histologic examinations. RESULTS: Sensitivity and specificity of detecting high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were higher for Pap smears than for HPV tests (sensitivity, 97.14%; specificity, 85.58% for Pap smears; sensitivity, 88.32%; specificity, 54.92% for HPV tests). HPV tests and Pap smears did not differ greatly in detection of low-grade squamous intraepithelial lesion (85.35% for HPV test, 80.31% for Pap smears). When atypical glandular cells were noted on Pap smears, the likelihood for histologic diagnosis of adenocarcinoma following Pap smear was higher than that of high-risk HPV test results (18.8 and 1.53, respectively). CONCLUSIONS: Pap smears were more useful than HPV tests in the diagnosis of HSIL, SCC, and glandular lesions.

Malignant peripheral nerve sheath tumor of the uterine cervix expressing both S-100 protein and HMB-45.

A 50-year-old woman presented with a large cervical polypoid mass. Grossly, the mass occupied a substantial proportion of the cervical canal, measuring 6 cm. Histologically, the mass showed a spindle cell malignancy arranged in large fascicles that penetrated deeply into the fibromuscular wall of the cervix. The spindle cells were immunoreactive for both S-100 protein and HMB-45 antigen, but were negative for Melan-A. Electron microscopy showed that cytoplasmic processes of the spindle to oval tumor cells contained microtubules and were lined by basal lamina and abundant intercellular collagen spacing with no melanosomes in any stage. As far as we are aware, this is the ninth reported case of cervical malignant peripheral nerve sheath tumor (MPNST), and the second reported case of MPNST expressing HMB-45 antigen.

Frozen Cytology of Meningeal Malignant Solitary Fibrous Tumor/Hemangiopericytoma.

A 51-year-old woman presented with severe dizziness. The brain magnetic resonance image revealed a 5.5 cm multiloculated mass with a thick rim in the left temporal lobe. Cytological examination of frozen diagnosis of the mass showed hypercellular sheets of round and rhabdoid cells in a hemorrhagic background, and two mitotic figures were observed. Histologically, the excised dura-based mass consisted of predominantly round cells with small foci of rhabdoid tumor cells in a pseudoalveolar pattern in a hemorrhagic background, and the cells showed nuclear positivity for signal transducer and activator of transcription 6 as well as frequent mitosis. The mass was diagnosed as a grade 3 solitary fibrous tumor (SFT)/hemangiopericytoma (HPC). The cytological diagnosis of SFT/HPC is challenging because of the heterogeneous cytological findings, such as histological heterogeneity, and because there are no standardized cytological criteria for malignant SFT/HPC. Cytological findings, such as singly scattered small cells, hypercellularity, rare ropy collagen, and round and rhabdoid cells with pseudoalveolar pattern, may assist in the diagnosis of malignant SFT/HPC.