Palisading Adenocarcinoma: A Morphologically Unique Salivary Gland Tumor With a Neuroendocrine-like Appearance and a Predilection for the Sublingual Glands of Women.

Adenocarcinoma, not otherwise specified (NOS) is a heterogenous group of salivary gland tumors that likely contains distinct tumors that have not yet been characterized. Indeed, in recent years, cases previously diagnosed as adenocarcinoma, NOS have been recategorized into novel tumor designations such as secretory carcinoma, microsecretory adenocarcinoma, and sclerosing microcystic adenocarcinoma. We sought to describe a distinctive, hitherto-undescribed salivary gland tumor encountered in the authors' practices. Cases were pulled from the surgical pathology archives of the authors' institutions. Histologic, immunohistochemical, and clinical findings were tabulated, and targeted next-generation sequencing was performed on all cases. Nine cases were identified, arising in 8 women and 1 man ranging from 45 to 74 years (mean, 56.7 y). Seven tumors (78%) arose in the sublingual gland, while 2 (22%) arose in the submandibular gland. The cases shared a distinctive morphologic appearance. They were biphasic, with ducts scattered among a predominant polygonal cell with round nuclei, prominent nucleoli, and pale eosinophilic cytoplasm. These cells were arranged as trabeculae and palisaded as pseudorosettes around hyalinized stroma and vessels, resembling a neuroendocrine tumor. Four of the cases were well-circumscribed, while the remaining 5 showed infiltrative growth including perineural invasion in 2 (22%) and lymphovascular invasion in 1 (11%). Mitotic rates were low (mean, 2.2/10 HPFs); necrosis was absent. By immunohistochemistry, the predominant cell type was strongly positive for CD56 (9 of 9) and variably positive for pan-cytokeratin (AE1/AE3) (7 of 9) with patchy S100 (4 of 9), but negative for synaptophysin (0 of 9) and chromogranin (0 of 9), while the ducts were strongly positive for pan-cytokeratin (AE1/AE3) (9 of 9) and CK5/6 (7 of 7). Next-generation sequencing did not reveal any fusions or obvious driver mutations. All cases were resected surgically, with external beam radiation also done in 1 case. Follow-up was available in 8 cases; there were no metastases or recurrences after 4 to 160 months (mean, 53.1 mo). A dual population of scattered ducts with a predominance of CD56-positive neuroendocrine-like cells characterizes a unique salivary gland tumor which is often encountered in the sublingual glands of women, for which we propose the term "palisading adenocarcinoma." Although the tumor was biphasic and had a neuroendocrine-like appearance, it lacked convincing immunohistochemical evidence of myoepithelial or neuroendocrine differentiation. Although a subset showed unequivocally invasive growth, this tumor appears to behave in an indolent manner. Moving forward, recognition of palisading adenocarcinoma and its separation from other salivary adenocarcinomas, NOS will facilitate a better understanding of the characteristics of this previously unrecognized tumor.

Liposarcoma of the pleural cavity.

Liposarcoma rarely occurs in the pleura or thoracic cavity, and few reports appear in the literature. We hypothesized that combining clinicopathologic, immunohistochemical, and fluorescence in situ hybridization methods would allow definite diagnoses. Using formalin-fixed, paraffin-embedded blocks, we examined 6 atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLPS), 5 dedifferentiated liposarcomas (DDLPSs), 2 pleomorphic liposarcomas, and 1 myxoid liposarcoma (MLPS). We used the Kaplan-Meier method and the Wilcoxon test for survival analysis for prognostic factor evaluation. Histologically, ALT/WDLPS was composed of a relatively mature adipocytic proliferation, accompanied by some lipoblasts. DDLPS exhibited round-to-oval tumor cells with a high nucleus-to-cytoplasm ratio that had proliferated in nests, accompanied in case 10 by some giant cells but no fatty cells. The pleomorphic type contained a varying proportion of pleomorphic lipoblasts. MLPS displayed uniform round- to oval-shaped cells and small signet-ring lipoblasts in a myxoid stroma. Immunohistochemically, 11 (79%), 11 (79%), and 10 (71%) of 14 cases were positive for S-100, p16, and CDK4, respectively. Six of the 14 cases (43%) were positive for MDM2 and adipophilin. One case of ALT/WDLPS and 3 cases of DDLPS exhibited MDM2 amplification by fluorescence in situ hybridization (Vysis LSI MDM2 SpectrumGreen Probe plus Vysis CEP 12 SpectrumOrange probe). ALT/WDLPS was the most favorable type for survival, while adipophilin tended to be a negative prognostic factor for pleural liposarcoma. For a firm diagnosis of liposarcoma in the pleura, immunohistochemistry for CDK4, MDM2, and adipophilin together with MDM2 gene amplification by fluorescence in situ hybridization may be an important diagnostic tool.

Potential of temperature-response collagen-genipin sol as a novel submucosal injection agent for endoscopic resection: Acute and chronic phase study using living animals.

OBJECTIVES: We proposed a novel temperature-response collagen sol as a submucosal injection agent for endoscopic resection (ER) using pepsin-solubilized collagen (PSC) and genipin (Ge) in a prior study. This study aimed to evaluate the usefulness and safety of the sol (PSC/Ge) in acute and chronic phase experiments using living animals. METHODS: In experiment 1, we performed endoscopic submucosal dissection (ESD) for six pigs using normal saline (NS), sodium hyaluronate (SH), and PSC/Ge. We compared the required amount of each agent per unit area and procedure time. In experiment 2, we created artificial ulcers with endoscopic mucosal resection (EMR) for five pigs using NS and PSC sol. We compared the artificial ulcer residual rate at 7 and 14 days after EMR, and the scarring rate at 14 days after EMR. RESULTS: The required amount of agents per unit area for PSC/Ge (0.8 ± 0.8 mL/cm2 ) and SH (1.1 ± 0.8 mL/cm2 ) were significantly smaller than that for NS (1.8 ± 0.7 mL/cm2 ). The total procedure time did not have a statistical difference. The artificial ulcer residual rates were 47.3 ± 0.7% for NS and 40.3 ± 0.7% for PSC/Ge on day 7 (P = 0.51), and 15.0 ± 0.1% for NS and 10.2 ± 0.1% for PSC/Ge sol on day 14 (P = 0.35). The scarring rate on day 14 was 10% for NS and 20% for PSC/Ge. CONCLUSION: We demonstrated the feasibility of a novel temperature-response collagen gel as a submucosal injection agent for ER in the acute and chronic phase animal experiment.

A novel pathogenic variant of the FH gene in a family with hereditary leiomyomatosis and renal cell carcinoma.

Hereditary leiomyomatosis and renal cell carcinoma caused by loss-of-function germline variants of the FH gene can develop into aggressive renal cell carcinoma (RCC). We report the case of a 27-year-old man who died of RCC. Genetic testing revealed a novel pathogenic variant of FH, NM_000143.3:c.1013_1014del (p.Ile338Serfs*3), that was also identified in healthy siblings. Identification of genetic causes in the proband helped us to provide relatives with precise genetic counseling and appropriate surveillance programs.

Effect of Stereotaxic Surgery of the Third Ventricle on Growth Performance in Neonatal Chicks.

Feeding behavior and energy metabolism are precisely regulated by humoral and/or neural factors in the central nervous system. In particular, nuclei, such as the arcuate nucleus, ventromedial hypothalamic nucleus, and lateral hypothalamic area located near the third ventricle of the hypothalamus are the centers of feeding and energy metabolism in various vertebrate species, including chickens. In this study, we evaluated the effects of cannulation of the third ventricle on chick growth and feeding behavior in the neonatal stage, to develop a method for local and chronic central nervous system-mediated energy metabolism. Referring to the chick brain atlas, a guide cannula was inserted into the third ventricle of the chick under anesthesia immediately after hatching using a stereotaxic instrument. The chicks that recovered from anesthesia were bred for 11 days under normal feeding management conditions, and then feed intake amount, body weight gain, and metabolic tissue weight were measured. The effects of direct stimulation of the third ventricle with 2-deoxy-D-glucose on the expression level of the immediate-early gene, cFOS, and feed intake in 5-day-old chicks were also evaluated. There were no differences in feed intake, body weight gain, and metabolic tissue weight between 11-day-old cannulated and control chicks. The expression of cFOS mRNA in the ventromedial hypothalamic nucleus was higher than that in the amygdala after the third ventricular administration of 2-deoxy-D-glucose. Additionally, direct third ventricular injection of 2-deoxy-D-glucose attenuated the feeding behavior of chicks for a while. Overall, we speculate that the technique is effective for local and/or chronic stimulation of the nucleus near the third ventricle of the chick hypothalamus, which is important for feed and energy metabolism regulation.

Glycyl-l-glutamine attenuates NPY-induced hyperphagia via the melanocortin system.

This study aimed to determine whether glycyl-l-glutamine (Gly-Gln; ß-endorphin (30-31)), a non-opioid peptide derived from ß-endorphin processing, modulates neuropeptide Y (NPY)-induced feeding and hypothalamic mRNA expression of peptide hormones in male broiler chicks. Intracerebroventricular injection of NPY (235 pmol) generated a hyperphagic response in ad libitum chicks within 30 min. Co-administration of Gly-Gln (100 nmol) attenuated this response, inducing a 30 % decrease. This was not attributable to Gly-Gln hydrolysis because co-administration of glycine (Gly) and glutamine (Gln) had no effect on NPY-induced hyperphagia. Gly-Gln injected alone also showed no effect. The hypothalamic pro-opiomelanocortin mRNA expression in the co-injection group was significantly higher than that in the NPY alone group. These data indicate that endogenous Gly-Gln may contribute to regulate feeding behavior via the central melanocortin system in chicks and acts as a counter regulator of the neural activity in energy metabolism.

Engrailed Homeobox 1 and Cytokeratin 19 Are Independent Diagnostic Markers of Eccrine Porocarcinoma and Distinguish It From Squamous Cell Carcinoma.

OBJECTIVES: The diagnostic utility of En1 in the histopathologic differentiation of eccrine porocarcinoma (EPC) from invasive squamous cell carcinoma (SCC) was investigated. METHODS: Expression of En1 and CK19 in 16 cases of EPC was immunohistochemically examined and compared with that in 32 cases of SCC. RESULTS: In all 16 EPCs, En1 was expressed in 3% to 100% of tumor cells. In 20 of the 32 SCCs, En1 was expressed in 3% to 90% of tumor cells. A total of 13 of the 16 EPCs and five of the 32 SCCs were judged as En1 positive, with a cutoff value of 25%. In addition, 11 of the 16 EPCs and four of the 32 SCCs were CK19 positive. The frequencies of En1- and CK19-positive cases were significantly higher in EPCs than in SCCs. In a logistic regression analysis for predicting EPC, En1 and CK19 were independent markers. When expression patterns of En1 and CK19 were combined, none of the 32 SCCs was both positive. In contrast, 15 of the 16 EPCs were positive for either En1 or CK19. CONCLUSIONS: A combination of En1 and CK19 expression can improve the accuracy of histologic diagnosis of EPC.

High-grade trichoblastic carcinoma arising through malignant transformation of trichoblastoma: Immunohistochemical analysis and the expression of p53 and phosphorylated AKT.

Trichoblastoma (TB) is a benign cutaneous adnexal neoplasm. The lesion typically presents as a slow-growing, solitary, well-circumscribed nodule measuring up to 3 cm in diameter. On rare occasions, TB causes malignant transformation into an aggressive form described as high-grade trichoblastic carcinoma. Four such cases have been reported to date; all were described as high-grade trichoblastic carcinomas. Here, we describe the case of a 72-year-old Japanese male patient with a rapidly enlarging subcutaneous tumor on his lower back, which was diagnosed as high-grade trichoblastic carcinoma. Histopathologically, the tumor featured both benign and malignant components, and a transition zone between these states was clearly evident. In the immunohistochemical analysis, a malignant component was positive for p53 and showed stronger staining of phospho-RAC-α serine/threonine-protein kinase (AKT) Ser473 in comparison with a benign component. These results suggest that loss of p53 function and activation of phosphatidylinositol 3-kinase-AKT signaling pathways played important pathogenic roles in malignant transformation of the present case.

Validation of treatment algorithm based on the Japan narrow-band imaging expert team classification for sub-centimeter colorectal polyps.

BACKGROUND AND STUDY AIMS: Although cold polypectomy (CP) is widely used for colorectal polyps < 10 mm, appropriateness of indications for CP or endoscopic mucosal resection (EMR) are still unclear. The aim of this study was to validate the endoscopic treatment algorithm based on the Japan NBI Expert Team (JNET) classification. PATIENTS AND METHODS: Consecutive patients with at least one colorectal non-pedunculated polyp < 10 mm between July 2014 and October 2016 were included in this retrospective study. During the period, EMR was performed for JNET ≥ 2B lesions and CP for JNET < 2A. Among a total of 3966 lesions, 3368 lesions with JNET ≤ 2A were resected by CP in compliance with the treatment algorithm but 565 resections for JNET ≤ 2A were not compliant (by EMR), while all 24 JNET > 2B lesions were removed by EMR in compliance with the algorithm. Polypectomy outcomes were compared between the compliant and non-compliant groups. Histological outcomes were analyzed in accordance with JNET classification. RESULTS: Post-polypectomy bleeding rate in the compliant group (0 %) was lower than that in the non-compliant group (0.53 %, P  < 0.01). Proportion of lesions diagnosed as cancer (38 % vs 0.36 %, P  < 0.01) or submucosal cancer (4.2 % vs 0.03 %, P  = 0.012), and the lesion with free resection margin (91 % vs 64 %, P  < 0.01) was higher in the JNET ≥ 2B than JNET ≤ 2A. CONCLUSION: This study indicated our algorithm would be valid: CP is suitable for most polyps < 10 mm as incidence of post-polypectomy bleeding is low, whereas EMR is recommended for JNET ≥ 2B lesions for histological complete removal.

FDG PET/CT Findings in a Localized Reactive Lymphoid Hyperplasia of the Spleen.

A 38-year-old man with sigmoid colon cancer underwent a preoperative contrast-enhanced CT which incidentally revealed a modestly enhancing splenic mass. FDG PET/CT showed mildly increased uptake in the splenic lesion in contrast to prominently increased uptake in the colonic tumor. In addition, the splenic mass demonstrated only slightly increased signal intensity in diffusion-weighted MRI, suggesting low probability of metastasis. Splenectomy nonetheless was performed at surgery of the colon cancer. The histopathologic examination showed aggregated lymphoid follicles with germinal centers in the splenic lesion and made the diagnosis of localized reactive lymphoid hyperplasia a rare benign lymphoid tumor.

Intimal Sarcoma of the Pulmonary Artery Treated with Pazopanib.

Intimal sarcoma is a rare disease with a poor prognosis. We herein report the case of a 71-year-old man with intimal sarcoma of the pulmonary artery treated with pazopanib. The tumor showed regression after 1 month of treatment. Hand-foot syndrome led to cessation of pazopanib, which triggered a disease flare. Pazopanib should be considered in patients with intimal sarcoma of the pulmonary artery that is unresectable or recurrent after surgery or cytotoxic chemotherapy. We must be careful about drug cessation, as it can lead to a disease flare.

A case of gastric adenocarcinoma of fundic gland type resected by combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET).

A male in his eighties attended our hospital for further evaluation of gastric cancer. A gastroscopy revealed a whitish flat elevated lesion (Paris, 0-IIa) of 15 mm in diameter on the greater curvature of the proximal fornix. The preoperative diagnosis was intra-mucosal differentiated gastric cancer, and a novel therapeutic approach, combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET) was applied and the lesion was resected in a single piece without any complications. Histopathological findings revealed atypical glandular epithelium proliferated in the mucosa and shallow layer (300 µm) of submucosa. These cells stained positive for pepsinogen-I and the final diagnosis was gastric cancer of fundic gland type (GAFT). There was no lymph-vascular involvement and free horizontal and vertical margins were confirmed. CLEAN-NET could be a therapeutic option for GAFT at low risk of lymph node metastasis because it prevents excess wall defect and exposure of cancer cells into the peritoneal cavity.

A genetically female brain is required for a regular reproductive cycle in chicken brain chimeras.

Sexual differentiation leads to structural and behavioural differences between males and females. Here we investigate the intrinsic sex identity of the brain by constructing chicken chimeras in which the brain primordium is switched between male and female identities before gonadal development. We find that the female chimeras with male brains display delayed sexual maturation and irregular oviposition cycles, although their behaviour, plasma concentrations of sex steroids and luteinizing hormone levels are normal. The male chimeras with female brains show phenotypes similar to typical cocks. In the perinatal period, oestrogen concentrations in the genetically male brain are higher than those in the genetically female brain. Our study demonstrates that male brain cells retain male sex identity and do not differentiate into female cells to drive the normal oestrous cycle, even when situated in the female hormonal milieu. This is clear evidence for a sex-specific feature that develops independent of gonadal steroids.

A subserosal uterus-like mass presenting after a sliding hernia of the ovary and endometriosis: a rare entity with a discussion of the histogenesis.

OBJECTIVE: To report the first case of a subserosal uterus-like mass. DESIGN: Case report. SETTING: A community-based hospital. PATIENT(S): A 44-year-old nulliparous woman who complained of a left inguinal mass had a medical history that was notable for two features. One was left oophorectomy for a sliding hernia at 10 months of age; the other was endometriosis at the oophorectomy site at 26 years of age. INTERVENTION(S): Tumorectomy. MAIN OUTCOME MEASURE(S): Not applicable. RESULT(S): Pathologic examination demonstrated that this subserosal mass mimicked a miniature uterus with a leiomyomatous lesion. CONCLUSION(S): As of September 2010, 23 cases of uterus-like mass had been reported. Three pathologic theories of uterus-like mass have been proposed: [1] congenital anomaly theory, [2] metaplasia theory, and [3] heterotopia. The pathogenesis of this rare entity is currently under debate. Most uterus-like masses have been connected to the genital organs (75.0%) and associated with endometriosis (50.0%). In the present case, the uterus-like mass developed at the surgical scar site of oophorectomy for a sliding hernia and a tumorectomy for endometriosis. We review the literature and discuss the theories regarding the histogenesis of uterus-like mass.

A Case of ST-elevated myocardial infarction resulting from obstructive intramural coronary amyloidosis.

A 49-year-old man presenting with ST-elevated myocardial infarction was brought to our emergency department with AL amyloidosis. Baseline coronary angiography showed no significant stenosis of the epicardial coronary arteries, however, coronary artery angiography in response to acetylcholine and coronary flow reserve in response to papaverine were abnormal, which suggested impairment of vascular endothelial function. Myocardial biopsy revealed amyloid deposition exclusively in intramural coronary arteries. Early amyloidosis without myocardial involvement can produce acute coronary syndrome through the combination of spastic epicardial coronary arteries and obstruction of the intramural coronary arteries. In the management of certain patients with acute coronary syndrome, the possibility of cardiac amyliodosis should be taken into consideration.

Follicular lymphoma with marked infiltration of eosinophils.

Eosinophilia and tissue infiltration by eosinophils are frequent findings in Hodgkin lymphoma, but they are extremely rare in B-cell lymphoma. Reported herein is a case of follicular lymphoma with extensive lymph node infiltration by eosinophils. The patient was a 71-year-old woman who had a mass in the vicinity of the pancreas found on routine ultrasonography. Subsequent CT indicated several enlarged abdominal lymph nodes, although superficial lymph nodes were not palpable. Two swollen mesenteric lymph nodes were excised to determine the cause of the lymphadenopathy. Histology indicated extensive infiltration of numerous eosinophils to the interfollicular area, especially in the dilated sinuses. The lymphoid follicles were relatively small, had inconspicuous germinal centers, and were scattered between dilated sinuses. Based on the histology, immunohistochemistry, and chromosomal abnormality, a diagnosis of follicular lymphoma was made. Expression of interleukin-3 (IL-3), IL-5, eotaxin, eotaxin-2, and eotaxin-3 was investigated on reverse transcription-polymerase chain reaction of the lymph node tissue, but none of the mRNA expression levels were elevated. This was a unique case of follicular lymphoma with extensive eosinophil infiltration, and to the best of the authors' knowledge this is the first such case ever reported.

Type AB thymoma accompanied by pure red cell aplasia and Good syndrome with CMV infection of tumor cells.

Reported herein is a case of type AB thymoma accompanied by pure red cell aplasia (PRCA) and Good syndrome. The patient was a 55-year-old woman who was found to be anemic and to have an abnormal shadow at the left pulmonary hilus on routine medical examination. Bone marrow aspiration was performed and she was diagnosed as having PRCA. She also had hypogammaglobulinemia. The anemia was temporarily cured with oral prednisolone and cyclosporin A, and the patient underwent total thymectomy. The tumor was type AB thymoma, composed mainly of type A components; widespread spindle cell components showed slight to moderate infiltration of immature T-cells. In addition, CMV inclusion bodies were scattered throughout this tumor. The CMV-infected cells were tumor cells, because they were positive for pancytokeratin and negative for CD34. Several cases of Good syndrome with widespread CMV infection have been reported, but it is extremely rare for CMV-inclusion bodies to be found in tumor cells. No thymoma cases involving CMV infection of tumor cells have been reported.