Ectopic adrenocorticotropic hormone syndrome caused by neuroendocrine carcinoma of the colon.

A 48-year-old woman with a history of autoimmune hemolytic anemia and taking long-term corticosteroid therapy presented with a 3-month history of general fatigue, abdominal distension, and pigmentation. A computed tomography scan of the abdomen showed a tumor in the sigmoid colon and multiple metastatic nodules in the liver. A colonoscopy revealed an obstructing mass with the presence of an irregular ulcer in the sigmoid colon. Following biopsy and histopathological analysis, the patient was diagnosed with neuroendocrine carcinoma (NEC) of the colon. She received her first cycle of chemotherapy, with carboplatin and etoposide. During hospitalization, her pigmentation and hypertension worsened and hypokalemia was observed, all of which suggsted Cushing's syndrome. Her plasma adrenocorticotropic hormone (ACTH) and cortisol levels were high, and an ectopic ACTH-producing tumor was suspected. After a second chemotherapy cycle, she developed neutropenic fever and subsequently died. At autopsy, two histological types were found in the tumor: small cell carcinoma and large cell NEC. Immunohistochemical analysis revealed ACTH in the large cell NEC. This is the first reported case of an ectopic ACTH syndrome caused by NEC of the colon.

Reactive Lymphoid Hyperplasia of the Liver Incidentally Found in a 55-Year-Old Woman with a History of Ulcerative Colitis.

Reactive lymphoid hyperplasia (RLH) is a benign disease, rarely occurring in the liver. Reactive immune phenomenon has been reported in association with its occurrence, but the true pathogenesis is unknown. No case was reported in association with inflammatory bowel disease. We report a case of RLH of the liver in a patient with ulcerative colitis (UC). A 55-year-old woman with UC went to the outpatient clinic with abdominal pain, and antibiotics were prescribed with diagnosis of acute appendicitis. Imaging study detected a mass in the liver but ruled out appendicitis. She was referred to our hospital for further examination after pain improving. A 12 mm hypoechoic mass was detected in the liver on ultrasonography. There were no typical malignant findings on computed tomography and magnetic resonance imaging. Regular image follow-up was recommended, but the patient strongly requested surgery because of family history of malignant disease. Laparoscopic partial hepatectomy was performed. Histopathological findings revealed a conglomerate hyperplasia of lymphoid follicles with germinal centers. Infiltrating lymphocytes were non-neoplastic. Final diagnosis was RLH of the liver. UC is chronic inflammatory bowel disease and may be related to RLH, but there is no clear explanation at this point. This is the first known reported case of RLH of the liver in a patient with UC. But the relationship between the RLH and UC remains uncertain. Further investigation and case accumulation are necessary.

Cerebellar outputs contribute to spontaneous and movement-related activity in the motor cortex of monkeys.

Cerebellar outputs originate from the dentate nucleus (DN), project to the primary motor cortex (M1) via the motor thalamus, control M1 activity, and play an essential role in coordinated movements. However, it is unclear when and how the cerebellar outputs contribute to M1 activity. To address this question, we examined the response of M1 neurons to electrical stimulation of the DN and M1 activity during performance of arm-reaching tasks. Based on response patterns to DN stimulation, M1 neurons were classified into facilitation-, suppression-, and no-response-types. During tasks, not only facilitation- and suppression-type M1 neurons, but also no response-type M1 neurons increased or decreased their firing rates in relation to arm reaching movements. However, the firing rates of facilitation- and suppression-type neurons were higher than those of no-response-type neurons during both inter-trial intervals and arm reaching movements. These results imply that cerebellar outputs contribute to both spontaneous and movement-related activity in the M1, which help to maintain muscle tones and execute coordinated movements, although other inputs also contribute to movement-related activity. Pharmacological inactivation of the DN supports this notion, in that DN inactivation reduced both spontaneous firing rates and movement-related activity in the M1.

Therapeutic Dilemma of Sarcoidosis and Treatment-naïve Hepatitis C Manifesting as Tattoo Reactions.

A 23-year-old man had an 8-day history of fatigue and dry cough and papulo-nodular reactions on his extensive tattoos. Chest radiography revealed several small granular shadows, and a transbronchial lung biopsy showed non-caseating epithelioid cell granuloma. A skin biopsy of the tattooed area showed histiocytic infiltrates with phagocytized tattoo pigment. Antibody tests for hepatitis C virus were positive. The patient was successfully treated with corticosteroid therapy, and after inflammation was suppressed, he received delayed anti-viral therapy. Sarcoidosis should be considered as a concurrent condition if papules are presented on the tattoos of patients with hepatitis C.

Scleredema with biopsy-confirmed cardiomyopathy: A case report.

Scleredema is a rare cutaneous mucinosis characterized by diffuse swelling and non-pitting induration. A 63-year-old man reported a 5-year history of skin thickening of the trunk and a 3-week history of dyspnea. Echocardiography revealed diffuse hypokinesis. Skin biopsies obtained from the waist showed thickened dermis with mucin. Myocardial biopsies showed alcian blue-stained tissue between the muscle fibers. The patient was referred to a dermatologist for phototherapy. Cardiomyopathy should be considered in patients with scleredema. Scleredema usually has a good prognosis; however, the mortality risk could be high when accompanied by cardiomyopathy.

Hemolytic Anemia in a Patient with Subacute Bacterial Endocarditis by Cardiobacterium hominis.

Hemolytic anemia is a rarely occurring manifestation of native valve infective endocarditis. We herein report an afebrile patient with hemolytic anemia caused by Cardiobacterium hominis endocarditis. A 60-year-old Japanese man had a history of aortic root replacement and the gradual onset of general fatigue. He had hemolytic anemia. Blood cultures detected C. hominis. A transthoracic echocardiogram showed aortic valve vegetation and periannular abscess with perforation of the non-coronary cusp. Intravascular hemolysis recovered after antimicrobial therapy, surgical removal of the vegetation and abscess, and aortic valve replacement. Subacute endocarditis should be considered if patients develop hemolytic anemia with signs of chronic inflammation without a fever.

Inflammatory disease and cancer with a decrease in Kupffer cell numbers in Nucling-knockout mice.

Nucling is a stress-inducible protein associated with apoptosomes. The cytochrome c-triggered formation of apoptosomes represents a key-initiating event in apoptosis. We have recently reported that Nucling regulates the apoptotic pathway by controlling the activation of NF-kappaB as well. Here we show that hepatocellular carcinoma (HCC) arising spontaneously against a background of hepatitis occurred more frequently in Nucling-knockout (KO) mice than wild-type (WT) mice. Biochemical serum testing revealed potential liver dysfunction with hypercholesterolemia in Nucling-KO males. In the background of Nucling-KO mice, we observed the up-regulation of TNFalpha, spontaneous NF-kappaB-activation and the induction of galectin-3 expression in liver. In addition, we observed a decrease in the number of Kupffer cells (KCs) in the KO mice. KCs are important for the hepatic immune system, acting as phagocytes or antigen-presenting cells (APCs). We found that KCs in Nucling-KO mice were apoptotic possibly through the up-regulation of TNFalpha. These observations indicate that Nucling is important for the regulation of NF-kappaB signals in liver. We propose that Nucling deficiency could be a powerful tool to reveal the NF-kappaB-related molecular networks leading to hepatitis and HCC development.

Potential pathophysiological role of D-amino acid oxidase in schizophrenia: immunohistochemical and in situ hybridization study of the expression in human and rat brain.

D-Amino acid oxidase (DAO) is a peroxisomal flavoenzyme that catalyzes oxidative deamination of a wide range of D-amino acids. Among the possible substrates of DAO in vivo, D-serine is proposed to be a neuromodulator of the N-methyl-D-aspartate (NMDA) type glutamate receptor. The gene for DAO was reported to be associated with schizophrenia. Since DAO is expected to be one of the key enzymes in the regulation of NMDA neurotransmission, the modulation of the enzyme activity is expected to be therapeutical for neuronal disorders. In search of the pathophysiological role of DAO, we analyzed the distribution of DAO mRNA and protein in the rat and human brain. In rat, the distribution of DAO mRNA was newly detected in choroid plexus (CP) epithelial cells in addition to glial cells of pons, medulla oblongata, and especially Bergmann glia of cerebellum. Moreover, to investigate how DAO expression level is altered in schizophrenia, we performed immunohistochemistry in the human brain. In agreement with the results in the rat brain, the immunoreactivity for DAO was detected in glial cells of rhombencephalon and in CP. Furthermore, higher level of DAO expression was observed in schizophrenic CP epithelial cells than that in non-schizophrenic cases. These results suggest that an increase in DAO expression in parts of the brain is involved in aberrant D-amino acid metabolism. In particular, gene expression of DAO in CP suggests that DAO may regulate D-amino acid concentration by modulating the cerebrospinal fluid and may be regarded as a potential therapeutic target for schizophrenia.

Endobronchial metastases 20 years after prostate cancer excision.

A 78-year-old Japanese man who had undergone total prostatectomy for prostate cancer (pT3cN1M0, Gleason score 3 + 3) 20 years previously was referred to the Respiratory Medicine Department of our institution because of a 1-week history of chest pain and cough. Computed tomography showed multiple small nodules and mediastinal lymph node enlargement. Bronchoscopy revealed multiple soft polypoid masses and obstruction of the lingular segment. Prostate-specific antigen (PSA) concentrations had increased markedly from 0.48 ng/mL in 2014 to 741 ng/mL in 2018. The diagnosis of prostatic cancer metastases was confirmed by revealing the presence of PSA via immunohistological staining of a bronchoscopically obtained biopsy of one of the masses. The patient had not been attending scheduled follow-up visits for the past 4 years. Treatment with degarelix (a gonadotropin-releasing hormone) was started, and the PSA concentration decreased dramatically (29 ng/mL). Metastases from prostate cancer are rarely first diagnosed two decades after radical prostatectomy. This patient illustrates the importance of obtaining a complete medical history.

Cholangiolocellular carcinoma containing hepatocellular carcinoma and cholangiocellular carcinoma, extremely rare tumor of the liver:a case report.

Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor which was first defined by Steiner, et al. in 1957 (1). CLC is thought to be derived from Hering's canal because tumor glands of CLC are morphologically similar to cholangioles. Recently, Theise, et al. reported that Hering's canal might be composed of hepatic stem cells (3). In addition, CLC sometimes contains a hepatocellular carcinoma (HCC) or cholangiocellular carcinoma (CCC) component within the tumor. Those findings suggest that CLC might originate from hepatic stem cells. On the other hand, because of its low frequency, clinicopatholigical features of CLC have not been fully clarified yet. We herein report a case of a 71-year old man with CLC. Based on preoperative imagings, the hepatic tumor was diagnosed as HCC, and he underwent a partial hepatectomy. The tumor contained both a HCC and CCC-like area. In immunohistochemistry, cytokeratin (CK) 7, CK20, CAM5.2 was positive, and CK19 was negative, therefore the tumor was diagnosed as CLC. The diagnostic criteria have not been described clearly, so CLC is difficult to diagnose preoperatively. Further studies are needed to clarify the clinical and clinicopatholigical features of CLC.

Malignant Brenner tumor with transition from benign to malignant components: computed tomographic and magnetic resonance imaging findings with pathological correlation.

We report computed tomographic and magnetic resonance findings of an ovarian malignant Brenner tumor with transition from benign to malignant components. The tumor was demonstrated as a cystic mass with solid mural components. The benign component contained dense calcifications on computed tomography and showed very low intensity on T2-weighted images, whereas the malignant component showed high intensity. The admixture of 2 components may well reflect the pathological feature and may be a diagnostic clue to malignant Brenner tumor.

Ovarian fibromatosis: magnetic resonance imaging findings with pathologic correlation.

Ovarian fibromatosis is a rare benign nonneoplastic condition with ovarian enlargement in young women and characterized by a proliferation of collagen-producing spindle cells surrounding normal ovarian structures. We reported magnetic resonance findings of a case that the affected ovarian parenchyma with follicles was surrounded by very low intense thick fibrous tissue on T2-weighted images such as "black garland" around the ovary. The magnetic resonance findings well reflected the pathological feature of the disease and may be diagnostic.

Double radiofrequency ablation is more extensive with a spherical zone shape compared to single ablation in a pig liver model.

OBJECTIVE: We compared the duration of ablation and the area of coagulation necrosis between a single ablation method (SAM) and a double ablation method (DAM) with a 'multitined expandable' electrode (LeVeen 2 cm) for radiofrequency ablation (RFA) using pig liver. METHOD: In the SAM group, ablation was completed after the first roll-off. In the DAM group, an additional ablation was performed to achieve a second roll-off. The comparison was made of the time required for roll-off and the extent of coagulation necrosis between the both groups. The Ellipticity index (EI) quantitatively describes the shape of the general RF ablation zone in the axial plane. RESULTS: There was no statistically significant difference in the interval until the first roll-off between both groups (SAM group: 100.7+/-24.7 seconds vs DAM group: 103.2+/-37.7 seconds, P=0.43). In the DAM group, the interval from the start of the additional ablation until the second roll-off was 154.0+/-86.9 seconds, longer than the interval for the first roll-off (P=0.023). The extent of coagulation necrosis was significantly more extensive in the DAM group (axial diameter, mean+/-SD, 26.2+/-2.8mm) x (maximal diameter: 29.3+/-1.6mm) x (minimal diameter: 26.5+/-3.6mm) compared to the SAM group with (23.0+/-3.3mm) x (23.7+/-3.1mm) x (20.0+/-2.5mm), respectively. Although there was no statistically significant difference in the EI between both groups, macroscopically, the shape of coagulation necrosis tended to be non-spherical in the SAM group and spherical in the DAM group. CONCLUSIONS: The DAM with a 'multitined expandable' electrode was more extensive with a spherical zone shape compared to the SAM.

Relationship between mucin expression and preoperative bile juice cytology in biliary tract carcinoma.

The present study evaluated correlations between preoperative bile juice cytology and mucin expression of surgical specimens in biliary tract carcinoma. Twenty-five patients with biliary tract carcinoma surgically treated at our hospital, whose bile juice cytology had been evaluated before operation, were allocated to this study. Biliary cytology was classified into three categories based on the Papanicolaou classification. Immunohistochemical staining of tissues was performed using MUC1 and MUC2 monoclonal antibodies. Lesions showing MUC1 expression of ++ or higher and MUC2 expression of - were classified as Group A, and the remaining lesions as Group B. According to the epithelial site, preoperative cytology was highly correlated in Group A, while it was negative in Group B (p<0.05). In the advanced site of carcinomas, preoperative cytology tended to highly be positive in Group A, while it tended to be negative in Group B (p<0.05). These results suggest that the bile juice cytology results are affected by characteristics of mucin expression in the tissue. Based on the possibility that mucin expression correlates with the prognosis of each carcinoma, a positive cytological result suggests a poor prognosis for the carcinoma, which may be informative for predicting the post-operative courses and choosing treatments.

A patient with spinal metastasis from hepatocellular carcinoma discovered from neurological findings.

Although spinal tumors are uncommon, they may reduce survival or cause serious functional disorders in the extremities. Metastatic spinal tumors from malignant tumors can induce symptoms of spinal cord compression, such as paraplegia, quadriplegia, and vesicorectal disturbance, which are aggravated with progression of the diseases and time. We report a patient with hepatocellular carcinoma (HCC) who was suspected of having spinal lesions based on neurological findings, and a metastatic spinal tumor was found by imaging examination. Assuming that metastasis had occurred at the time lumbar pain developed, the patient reached the level of gait disturbance within only 4 mo, showing a rapid advancement of symptoms. If early diagnosis had been possible, treatment could be performed before acute myelopathy progressed to complete paralysis. We speculate that the terminal stage of HCC is not only liver failure associated with intrahepatic lesions but also metastasis to other regions, treatment for individual pathologies therefore, will be needed, which constitutes an important issue.

Primary pulmonary malignant peripheral nerve sheath tumor: a case report.

BACKGROUND: Although the histologic features of malignant peripheral nerve sheath tumor (MPNST) have been described, the cytologic features of primary pulmonary MPNST have not been reported in the literature. CASE: We report a case of primary pulmonary MPNST in a 78-year-old man. Follow-up computed tomography of colon cancer, renal cancer, penile cancer and gingival cancer revealed a nodular lesion, 12 mm in diameter, in the right upper lobe of the lung. In frozen section, a diagnosis of malignant neoplasm, not otherwise specified, was rendered for the imprinting specimen and histologic specimen. Imprinting specimens were composed of small cellular aggregates and discohesive neoplastic cells with obvious malignant features. Histologically, spindle cells with pleomorphic nuclei arranged infascicular patterns and multinucleated tumor giant cells were also observed. More than 25 mitotic figures were observed per 10 high-power fields. Tumor cells were positive only for vimentin and S-100, and the Ki-67 labeling index was 10%. Clinical and imaging investigation failed to identify an alternative primary site. We histologically diagnosed this case as primary pulmonary MPNST. CONCLUSION: MPNST has a varied cytomorphology with frank nuclear atypia showing no definite differentiation. Multinucleated neoplastic giant cells with immunopositivity for S-100 may permit more accurate diagnosis of MPNST.

False-positives in fine-needle aspiration cytology of breast disease can be reduced with p63 immunostaining--a preliminary report.

Myoepithelial cells of the mammary gland are considered to be a key to distinguishing benign from malignant disease in fine-needle aspiration (FNA) cytology. However, identification of these cells with Papanicolaou staining is not easy. The identification of myoepithelial cells was investigated using p63 antibodies to carry out immunostaining of FNA specimens that had been used at the time of Papanicolaou staining for 37 patients who yielded false-positives in FNA. Positively-stained cells were observed in overlying cell clusters or the background in 67.6% of the patients. There is a possibility that over-diagnosis could have been avoided by performing p63 staining for these patients. The controls consisted of stamp samples of fresh specimens obtained from 23 patients at the time of surgery for invasive carcinoma and the results of p63 immunostaining did not reveal any positive staining of tumor cells. Accordingly, these results indicate that there is a strong likelihood that there is no invasive carcinoma when many p63-positive cells are observed in the tumor cell population or the background and that p63 immunostaining has the potential to aid in reducing false-positives at the time of FNA diagnosis of breast disease.

Rapid-growing solitary necrotic nodule of the liver.

The solitary necrotic nodule of the liver is an uncommon nonmalignant lesion with an uncertain etiology. The lesion was defined as a nodule with a completely necrotic core and fibrous capsule etc. and without a consistency of viable cells. The characteristic features of this benign lesion on the imaging modalities are similar to the metastatic tumor. In this paper we discuss the case of a rapid-growing solitary necrotic nodule of the liver occurring in a patient with chronic renal failure on hemodialysis. The lesion located on the left median lobe of the liver had rapidly enlarged in diameter in the last seven months. Despite some examinations by imaging modalities to confirm the preoperative diagnosis, we were unable to visually confirm. Several histological examinations using a needle biopsy specimen were performed, but the diagnosis was all necrotic tissue. However, we recommended an extended left hepatic lobectomy for this rapid-growing lesion since cholangiocarcinoma with necrosis could be hardly differentiated. Permanent histology revealed that the lesion was solitary necrotic nodule. We consider that permanent histology of the entire lesion is possibly the only accurate method of diagnosis. Since the solitary necrotic nodule does not indicate malignancy, hepatic resection should be performed.