Two cases of prostate cancer with disseminated carcinomatosis of the bone marrow treated with novel hormonal agents.

Introduction: Disseminated carcinomatosis of the bone marrow in prostate cancer is rare and has a poor prognosis. Although strong evidence suggests that novel hormonal agents improve the prognosis of metastatic prostate cancer, their effectiveness in cases of disseminated carcinomatosis of the bone marrow remains unclear. Case presentation: We encountered two cases of prostate cancer with disseminated carcinomatosis of the bone marrow at the time of initial diagnosis. One patient was treated with enzalutamide, abiraterone, docetaxel, cabazitaxel, denosumab, and radium-223 and died 38 months after the initial diagnosis. The other patient was treated with apalutamide and denosumab, and had progression-free survival for 17 months after the initial diagnosis. Conclusion: These results suggest that novel hormonal agents may improve the prognosis of prostate cancer even in patients with disseminated carcinomatosis of the bone marrow.

Histopathological Evaluation of Pulmonary Thromboendarterectomy Specimens of Chronic Thromboembolic Pulmonary Hypertension.

AIMS: Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition with a poor prognosis in which the pulmonary arteries are occluded by organized thrombi. Pulmonary thromboendarterectomy (PEA) is an effective treatment for CTEPH; however, the literature on its histopathological examination is lacking. This study aimed to investigate the histopathological findings and protein and gene expression in PEA specimens, establish an optimal histopathological evaluation method, and clarify the mechanisms of thrombus organization and disease progression in CTEPH. METHODS: In total, 50 patients with CTEPH who underwent PEA were analyzed. The patients were categorized according to their clinical data into two groups: good and poor postoperative courses. The relationship between their histopathological findings and the clinical course was examined. Immunohistochemical studies confirmed the expression of oxidants, antioxidants, and smooth muscle cell (SMC) differentiation markers and their changes during the progression of thrombus organization. The mRNA expression analysis of 102 samples from 27 cases included oxidants, antioxidants, and vasoconstrictor endothelin-1. RESULTS: In the PEA specimens, colander-like lesions (aggregations of recanalized blood vessels with well-differentiated SMCs) were significantly more common in the good postoperative course group than in the poor postoperative course group; analysis of proteins and genes proposed that oxidative and antioxidant mechanisms were involved. In the colander-like lesions, there was an increase in endothelin-1 mRNA and protein expression of endothelin receptor A. CONCLUSIONS: Colander-like lesions in PEA specimens must be identified. Additionally, SMC differentiation in recanalized vessels and the expression of vasoconstrictors and their receptors may contribute to the progression of CTEPH.

Relationship between the aortic root Z-score and degree of translamellar mucoid extracellular matrix accumulation.

PURPOSES: A retrospective analysis was performed to compare the pathological findings and aortic root Z-score in patients with and without connective tissue disease (CTD). METHODS: Twenty-two patients {47.5 [15-85] years old, 18 males} underwent surgery for aortic root dilatation without aortic dissection: 10 {40 [16-59] years old} with CTD and 12 {57.5 [15-85] years old} without CTD (non-CTD; p = 0.049). Systemic hypertension (p = 0.043) and the degree of preoperative aortic regurgitation (p = 0.017) were higher in the non-CTD patients than in the CTD patients. RESULTS: The diameters of the sinotubular junction (STJ) (p = 0.048) and ascending aorta (Asc.Ao.) (p = 0.020) and the Z-scores of the STJ (p = 0.027) and Asc.Ao. (p = 0.009) were significantly higher in the non-CTD patients than in the CTD patients. The degree of translamellar mucoid extracellular matrix accumulation (T-MEMA) of the Asc.Ao. was significantly higher in the non-CTD patients than in the CTD patients (p = 0.037) and was significantly correlated with the Z-scores of the aorta (R = 0.746, p < 0.01 in the sinus of Valsalva and R = 0.382, p = 0.031 in the Asc.Ao.), although there was no significant correlation between the diameter of the STJ and that of Asc.Ao. CONCLUSIONS: In non-CTD patients, not only the aortic root but also Asc.Ao. tended to dilate with age, and a significant correlation between the Z-scores of the aorta root and the Asc.Ao. and the degrees of T-MEMA was observed.

Rosai-Dorfman disease of thymus with elevated serum anti-acetylcholine receptor antibody: a case report.

Rosai-Dorfman disease is a rare disorder of histiocytic proliferation in lymph nodes and at extranodal sites. We herein describe a patient with isolated Rosai-Dorfman disease in the thymus with elevated anti-acetylcholine receptor antibody. We examined the relationship between Rosai-Dorfman disease and elevated anti-acetylcholine receptor antibody. To our knowledge, elevated anti-acetylcholine receptor antibody has not been reported in isolated thymic Rosai-Dorfman disease.

Chronic Thromboembolic Pulmonary Hypertension Complicated by Giant Pulmonary Artery Aneurysm.

A pulmonary artery (PA) aneurysm is an extremely rare condition that can be idiopathic or secondary. Only a few reports on giant PA aneurysms associated with chronic thromboembolic pulmonary hypertension (CTEPH) are available in the literature. Here, we present a case of CTEPH associated with a secondary giant PA aneurysm detected by autopsy. A 68-year-old woman was diagnosed with pulmonary hypertension (PH) and a PA aneurysm with a diameter of 7.5 cm 7 years before admission. CTEPH was suspected as the cause of PH; however, she refused to undergo surgical treatment. Although her condition improved temporarily with pulmonary vasodilators, she had recurrence of heart failure and died because of the deterioration of her general condition. An autopsy revealed a giant PA aneurysm without medial degeneration, suggesting a secondary PA aneurysm associated with PH. Histological findings indicated multiple organized thrombi with recanalization in the PA bilaterally, and CTEPH was diagnosed as the cause of PH. Although rare, when a PA aneurysm is detected, it is important to consider that CTEPH might be associated with a giant PA aneurysm. A better understanding of this condition is necessary to improve the therapeutic strategy.

Giant cell arteritis in a patient with aortic dissection: a case report.

Aortic lesions, such as an aortic aneurysm, are known as a late complication that usually occurs several years after the onset of giant cell arteritis. Here, we report a rare case of large-vessel giant cell arteritis in a patient with aortic dissection. A 71-year-old man presented with acute back pain and was diagnosed with aortic dissection, Stanford type A, and he underwent elective ascending aortic replacement. Further studies showed that the resected ascending aorta had aortic dissection and multinucleated giant cell granulomas; the granulomas were located in the media near the intima with partial destruction of the internal elastic lamina; there was no stenosis of the feeding blood vessel or fibrosis of the adventitia as observed in Takayasu arteritis; other types of vasculitis were considered unlikely based on the symptoms and laboratory data. The patient was further diagnosed with giant cell arteritis, which was classified as a large vessel vasculitis along with Takayasu arteritis at the Chapel Hill Consensus Conference in 2012. This is a rare case of giant cell arteritis diagnosed in a patient with aortic dissection. The differences in histopathological findings between Takayasu arteritis and giant cell arteritis are discussed.

[A Case of Performed Right Colectomy with Pancreato-Duodenectomy for Transverse Colon Cancer Invased to Duodenum].

There is a clear consensus regarding the combined resection of organs with cancer invasion, patients with colon cancer. However, there are very few reports to our knowledge regarding the use of pancreato-duodenectomy(PD)for colon cancer patients with cancer invasion in the duodenum. We here report a colon cancer patient in whom we performed PD and right hemicolectomy, who showed favorable results with no recurrence. The patient was a 69-year-old woman. Her chief complaint was hypogastric pain. Her previous doctor performed colonoscopy and a colonoscopic biopsy, and detected a type 2 lesion, throughout the entire circumference of the transverse colon near the liver, and she was diagnosed with adenocarcinoma. From further imaging analyses, she was diagnosed as having transverse colon cancer with invasion into the superior mesenteric vein(SMV), duodenum, and pancreatic head, and No. 223 lymph node metastasis. The patient's cancer was concluded to be unresectable, and she underwent chemotherapy, namely mFOLFOX6 with cetuxiumab(Cmab). One course of mFOLFOX with Cmab, the patient decided to consult our hospital for a second opinion. We concluded that her cancer was resectable, so we performed PD, right hemicolectomy, and resection and reconstruction of a part of the SMV. The operation time was 5 hours 17 minutes, and total blood loss was 190 mL. The histopathological diagnosis was tub2, T4b(duodenum and, tissue surrounding the SMV), int, INF b, ly1, v2, PN1b, EX(+)/ND(PN+, v+), PM0(25 cm), DM0(14.3 cm), N1(1/ 20), H0, P0, M0, pStage III a. She was discharged 15 days after surgery with no complications, and thereafter received ajduvant chemotherapy(capecitabine with oxaliplatin)as an outpatient. After 3 courses, capecitabine with oxaliplatin was changed to capecitabine because she developed a nervous system disorder, and she was further treated for approximately about 6 months. She is doing well at the time of writing, with no recurrences for 2 years. We suggest that PD should be performed on colon cancer patients in which the colon cancer has invaded other organs and has been evaluated as being unresectable.

Cytological features of mammary analogue secretory carcinoma of salivary gland: fine-needle aspiration of seven cases.

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland neoplasm that is defined by ETV6-NTRK3 gene fusion. There have been few case reports on the cytopathologic features of MASC to date. We examined the clinicopathological and cytological features of seven cases of MASC defined by RT-PCR analysis of the ETV6-NTRK3 fusion gene. The cases occurred in three men and four women aged between 39 and 68 years, with a mean of 51.6 years. In five of these seven cases, the tumor involved the parotid gland. Histologically, all cases displayed predominantly microcystic patterns, often a mixture of follicular and papillary-cystic structures. All tumors were immunoreactive for mammaglobin, S-100 protein, and vimentin. Available fine-needle aspiration cytology smears were cellular and exhibited many loosely cohesive syncytial clusters or isolated cells. Many histiocytes, some of which contained hemosiderin pigments, and variously shaped mucinous material were evident in the background or within the epithelial clusters. The majority of cases showed small to medium-sized follicular structures with secreted materials. Papillary clusters were occasionally found. Tumor cells exhibited small to medium-sized round to oval nuclei, with a smooth contour and indistinct or small nucleoli, and vacuolated cytoplasm. No tumor cells had obvious intracytoplasmic zymogen granules. It appeared that clusters of small to medium-sized follicular and papillary configurations consisting of bland tumor cells with vacuolated cytoplasm, but lack of intracytoplasmic zymogen granules, in a mucinous or hemosiderin-laden histiocyte-rich background, were a characteristic cytological feature highly suggestive of MASC.

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.

Effect of endothelial cell proliferation on atherogenesis: a role of p21(Sdi/Cip/Waf1) in monocyte adhesion to endothelial cells.

OBJECTIVE: Uniform laminar shear stress (LS) and disturbed turbulent shear stress (DS) are thought to play opposite roles in preventing or inducing atherosclerosis. Endothelial cell (EC) growth and monocyte adhesion to ECs, an early event in atherosclerosis, are also oppositely regulated by LS and DS. However, how atherogenesis is affected by the regulation of growth by blood flow is unknown. Here we examined the role of p21(Sdi/Cip/Waf1) (p21), a growth inhibitor induced by LS, in monocyte adhesion to ECs. METHODS: p21 was overexpressed by transfecting a p21-expressing adenoviral vector into ECs. Factors linking EC growth, monocyte adhesion, and p21 were examined by microarray analysis, PCR and Western blotting. RESULTS: Compared with DS, in the presence or absence of TNFalpha, LS significantly inhibited EC growth and monocyte adhesion to ECs. Both EC proliferation and monocyte adhesion induced by DS were inhibited by p21-overexpression. LS suppressed the expression of thioredoxin-interacting protein (TXNIP). Thioredoxin (TRX) activity, which is suppressed by TXNIP, was therefore higher under LS than DS, as reported previously. p21-overexpression significantly suppressed the DS-induced TXNIP expression, and inhibited the expression of vascular cell adhesion molecule 1 and chemokine (C-C motif) ligand 5 (CCL5/RANTES), which stimulates leukocyte recruitment and is downregulated by ROS scavenging. CONCLUSION: p21 may function to prevent atherogenesis by regulating the redox balance, which leads to the inhibition of adhesion molecule and chemokine expression in ECs under LS.

Inflammatory pseudotumor (inflammatory myofibroblastic tumor) of the mitral valve of the heart.

We report a rare case of inflammatory pseudotumor/inflammatory myofibroblastic tumor (IPT/IMT) of the heart, involving the mitral valve. A 58-year-old woman presenting with dyspnea was immediately admitted to the hospital, and found to have congestive heart failure due to the invagination of a tumor-like mass of the mitral valve. This mass arose from and involved almost the entire posterior leaflet of the mitral valve and occupied almost the entire mitral valve orifice. The tumor was a yellowish-white well-circumscribed mass with a smooth surface. The excised mass was 3.0 x 2.3 x 1.8 cm, and consisted of abundant Sudan III-positive foam cells, histiocytes, lymphocytes, plasma cells, and loosely arrayed spindle cells, in vascular-rich fibrous tissue. Immunohistochemistry showed that the spindle cells were positive for vimentin and alpha-smooth muscle actin, and negative for desmin, CD34, and human muscle actin (HHF-35), suggesting they were myofibroblastic cells. The plasma cells and lymphocytes showed no monoclonality. There were few mitotic cells, and, except for the lymphocytes, few Ki-67-positive cells. The findings suggested IPT/IMT. The 39 cardiac IPT/IMT cases appearing in the English-language literature are discussed.

Aryl hydrocarbon receptor mediates laminar fluid shear stress-induced CYP1A1 activation and cell cycle arrest in vascular endothelial cells.

AIMS: We investigated the mechanisms of shear stress (SS)-induced activation of cytochrome P450 (CYP) 1A1 and cell cycle arrest with regard to the role of the aryl hydrocarbon receptor (AhR), since AhR mediates the expression of CYP1A1 induced by polycyclic aromatic hydrocarbons (PAHs) and is thought to be involved in the regulation of cell growth and differentiation. METHODS AND RESULTS: Human umbilical vein endothelial cells (ECs) were exposed to laminar SS and thereafter collected to evaluate the expression, activity, and transcription of CYP1A1 and the expression of AhR and cell cycle-related proteins. A physiological level of laminar SS (15 dynes/cm(2)) markedly increased the expression level and enzymatic activity of CYP1A1. SS stimulated CYP1A1 promoter activity without influencing mRNA stability. Loss of two functional xenobiotic response elements (XREs) in the 5'-flanking region of the CYP1A1 gene suppressed the SS-induced transcription of CYP1A1. Laminar SS stimulated the expression and nuclear translocation of AhR. alpha-Naphthoflavone, an AhR antagonist, and a small interfering RNA (siRNA) for AhR significantly suppressed SS-induced CYP1A1 expression. The siRNA also abolished SS-induced cell cycle arrest, the expression of the cyclin-dependent kinase inhibitor p21(Cip1), and dephosphorylation of retinoblastoma protein. CONCLUSION: Laminar SS stimulated the transcription of CYP1A1 through the activation of AhR in a way that is similar to the effects of PAHs. AhR was also involved in cell cycle arrest induced by SS. Our results suggest that sustained activation of AhR exposed to blood flow plays an important role in the regulation of EC functions.