Clinicopathological analysis of clinically occult extrapulmonary lymphangioleiomyomatosis in intra-pelvic and para-aortic lymph nodes associated with pelvic malignant tumors: A study of nine patients.

The clinicopathological and immunohistochemical characteristics of clinically occult extrapulmonary lymphangioleiomyomatosis in lymph nodes (LN-LAM) being dissected during surgical staging of pelvic malignancy have not been well investigated. We assessed samples from nine female patients (median age, 61). None had past or familial history of tuberous sclerosis and had LAM lesions other than LN such as lung. The primary malignancies included four endometrial endometrioid carcinomas, one endometrial carcinosarcoma, three ovarian serous carcinomas and one urothelial carcinoma. Median follow-up was 43 months. The number of affected LNs ranged from 1 to 15 (median, 2) with sizes ranging from 1 to 13 mm (median, 3.0). Six cases had clinically occult LN-LAM only within the pelvic LNs, two only within para-aortic LNs, and one within both pelvic and para-aortic lymph nodes. Immunohistochemically, LAM cells exhibited a strong diffuse positivity for ß-catenin and E-cadherin in all nine cases. Clinically occult LN-LAM mainly affects peri- or post-menopausal women. On rare occasions, occult LN-LAM may manifest as systemic LAM, including in the lung. ß-catenin and E-cadherin carry potential utility as additional diagnostic markers.

Room Temperature Decarboxylative and Oxidative [2+2+2] Annulation of Benzoic Acids with Alkynes Catalyzed by an Electron-Deficient Rhodium(III) Complex.

It has been established that an electron-deficient (η5 -cyclopentadienyl)rhodium(III) [CpE RhIII ] complex is capable of catalyzing the decarboxylative and oxidative [2+2+2] annulation of benzoic acids with alkynes to produce substituted naphthalenes at room temperature. The appropriate choice of the additive and the solvent is crucial for this transformation. This catalyst system allowed use of oxygen as a terminal oxidant and broadened the substrate scope including both aromatic and aliphatic alkynes. In this catalysis, the electron deficient nature of the CpE RhIII catalyst would cause the strong rhodium-π interaction, which accelerates the decarboxylation as well as the C-H bond cleavage.

[Mucinous Tubular and Spindle Cell Carcinoma in a Patient on Hemodialysis : A Case Report].

Although patients on long-term hemodialysis frequently develop renal cell carcinoma, mucinous tubular and spindle cell carcinoma (MTSCC) is rare in incidence. Here, we report a case of MTSCC occurring in a patient under hemodialysis. The patient was a 72-year-old man with end stage renal failure due to diabetic nephropathy. Hemodialysis was initiated in 2003. He presented with macrohematuria. Contrastenhanced computed tomography (CT) revealed a right renal tumor. Laparoscopic right nephrectomy was performed accordingly in June 2017. Pathologically, the tumor was diagnosed as MTSCC. Six months after the surgery, the patient remains free of recurrence and metastasis. Here we review the characteristics of 5 MTSCC cases in patients on hemodialysis reported in Japan.

Oxidative Annulation of Arenecarboxylic and Acrylic Acids with Alkynes under Ambient Conditions Catalyzed by an Electron-Deficient Rhodium(III) Complex.

It has been established that an electron-deficient Cp(E) rhodium(III) complex catalyzes the oxidative [4+2] annulation of substituted arenecarboxylic and acrylic acids with alkynes under ambient conditions (at RT-40 °C, under air) without using excess amounts of substrates to produce the corresponding substituted isocoumarins and α-pyrones in high yields. Minor modification of reaction conditions depending on the coordination ability of alkynes realized the high efficiency.

Clinicopathologic features of autosomal recessive amyotrophic lateral sclerosis associated with optineurin mutation.

We performed clinicopathological analyses of two amyotrophic lateral sclerosis (ALS) patients with homozygous Q398X optineurin (OPTN) mutation. Clinically, both patients presented signs of upper and lower motor neuron degeneration, but only Patient 1 showed gradual frontal dysfunction and extrapyramidal signs, and temporal lobe and motor cortex atrophy. Neuropathological examination of Patient 1 revealed extensive cortical and spinal motor neuron degeneration and widespread degeneration of the basal ganglia. Bilateral corticospinal tracts exhibited degeneration. Loss of spinal anterior horn cells (AHCs) and gliosis were observed, whereas posterior columns, Clarke's columns, intermediate lateral columns, and the Onuf's nucleus were spared. In the brainstem, moderate neuronal loss and gliosis were noted in the hypoglossal and facial motor nuclei. No Bunina bodies were found in the surviving spinal and brainstem motor neurons. Transactivation response (TAR) DNA-binding protein 43 (TDP-43)-positive neuronal and glial cytoplasmic inclusions were observed throughout the central nervous system. The Golgi apparatus in motor neurons of the brainstem and spinal cord was often fragmented. Immunoreactivity for OPTN was not observed in the brain and spinal cord, consistent with nonsense-mediated mRNA decay of OPTN. The TDP-43 pathology of Q398X was similar to that of an autosomal dominant E478G mutation. This result suggests that the loss-of-function, but not the proteinopathy itself, of OPTN results in TDP-43 deposits in neuronal and glial cytoplasm and Golgi apparatus fragmentation, leading to multisystem neurodegeneration.

A Case of Multiple Brain Tuberculomas in the Subarachnoid Cisterns: Recognition of Radiological Characteristics Regarding the Development of Paradoxical Response during Antituberculosis Treatment.

Brain tuberculoma and its occurrence within the subarachnoid cisterns is rare in Japan. Serological and cerebrospinal fluid (CSF) examinations and imaging findings lack specificity; thus, preoperative diagnosis is often challenging. This report presents the case of a 70-year-old woman admitted to our hospital with a one-month history of low-grade fever and altered mental status. Based on the CSF analysis and her history of latent tuberculosis infection seven years ago, she was strongly suspected of suffering from tuberculous meningitis (TBM). Consequently, the patient was enrolled in a clinical trial for antituberculosis treatment (ATT). CSF soluble interleukin-2 receptor level decreased from 2,926 U/mL on day 1 to 225 U/mL 42 days after initiating ATT. Her condition improved after five weeks; however, contrast-enhanced T1-weighted magnetic resonance imaging (MRI) revealed multiple enhanced lesions within the basal subarachnoid cisterns 25 days after admission. As the number and size of these lesions increased, a biopsy confirmed brain tuberculoma diagnosis, and the treatment was continued. In conclusion, when intracisternal scattered mass lesions are identified during TBM treatment, we should consider the possibility of tuberculoma developments arising from a paradoxical response (PR) during the treatment. Serial MRIs are crucial in monitoring PR development in cisternal tuberculomas, an extension of severe TBM. Finally, a PR can be effectively managed by continuing ATT with adjunctive corticosteroids.

Acute hemorrhagic cholecystitis related to diffuse neurofibroma of gallbladder in a patient with neurofibromatosis type 1.

BACKGROUND: We report the first case of acute hemorrhagic cholecystitis with large hemoperitoneum related to gallbladder wall fragility caused by neurofibroma cell infiltration. CASE PRESENTATION: A 46-year-old man with neurofibromatosis type 1 (NF1), who had been hospitalized for retroperitoneal hematoma and treated by transarterial embolization 9 days earlier, complained of right upper quadrant pain, bloating, nausea, and emesis. Computed tomography revealed fluid collection and a distended gallbladder with high-density contents. The patient was taken to the operating room for laparoscopic cholecystectomy, with consideration of the hemodynamic tolerance, for acute hemorrhagic cholecystitis. An initial laparoscopy revealed a significant amount of blood in the abdominal cavity exuding from the gallbladder. Due to its fragility, the gallbladder was easily ruptured by surgical manipulation. After conversion to open surgery, subtotal cholecystectomy was performed. Seventeen days after surgery, the patient was transferred to another hospital for rehabilitation. Histological examination revealed diffuse and nodular proliferation of spindle cells that had replaced the muscularis propria of the gallbladder wall. CONCLUSION: This clinical case highlights how NF1 can cause various symptoms in the blood vessels and gastrointestinal tract, including the gallbladder.

Di- and trinuclear sandwich complexes of a cross-conjugated fulvene.

We report di- and trinuclear palladium sandwich complexes of cross-π-conjugated fulvenes. Structural and theoretical analysis revealed that a fulvene sandwich framework holds a metal-metal bonded moiety, where the dinuclear and trinuclear bonds feature strong donation and back-donation, respectively. The trinuclear fulvene sandwich complex undergoes a unique reversible extrusion of a Pd atom from inside to outside the sandwich framework.

Leptomeningeal carcinomatosis in small cell carcinoma of the prostate.

Introduction: Leptomeningeal carcinomatosis in small cell carcinoma of the prostate is rare. Case presentation: A 69-year-old man visited our hospital due to dysuria and edema. Bilateral hydronephrosis and lymph node metastases due to a pelvic tumor were observed. Although the prostate-specific antigen level was normal, the tumor was suspected to originate from the prostate. He underwent percutaneous nephrostomy and prostate biopsy. Histopathology revealed small cell carcinoma accompanied by increased pro-gastrin-releasing peptide and neuron-specific enolase levels. After receiving systemic chemotherapy with carboplatin and etoposide and radiation therapy for prostate, these lesions gradually decreased in size, and tumor markers normalized. Ten months after the initial diagnosis, he developed consciousness disorder and seizure. Magnetic resonance imaging revealed leptomeningeal carcinomatosis without any other recurrences and elevated tumor markers. He died 4 weeks after these symptoms appeared. Conclusion: Careful monitoring of the central nervous system should be considered in small cell carcinoma of the prostate patients.

Poor Outcome due to the Plasmacytoid Variant of Urothelial Carcinoma.

A 72-year-old man visited our hospital due to pollakiuria and lower abdominal pain. Urinary cytology was positive, and cystoscopy revealed diffuse edematous nonpapillary tumor. We performed transurethral biopsy, and clinical stage T3 plasmacytoid variant of urothelial carcinoma (PUC) was diagnosed. Although we planned for radical cystectomy, peritoneal dissemination and lung and pelvic lymph node metastases appeared 3 weeks after the initial visit. We also planned for chemotherapy; however, the metastases rapidly progressed, and he died 7 weeks after the biopsy. PUC is rare and shows an aggressive clinical course and poor prognosis.

Micropapillary Variant of Urothelial Carcinoma in a Hemodialysis Patient.

The micropapillary variant of urothelial carcinoma (MPUC) is an aggressive form of urothelial carcinoma with high metastatic potential and a poor prognosis. Although various therapies have been reported, there is still no established treatment strategy for MPUC due to its rarity. The incidence of urinary tract malignancies is higher in patients undergoing hemodialysis (HD) than in healthy individuals. Here, we report the case of an 82-year-old man on HD with end-stage kidney disease who visited our hospital for macrohematuria. Cystoscopy followed by computed tomography and urine cytology revealed a sessile papillary tumor around the left bladder wall. We performed transurethral resection of the bladder tumor. Based on histopathological and imaging findings indicative of clinical-stage T3N0M0 MPUC, we performed radical cystectomy. Histopathology revealed a pathological stage T4aN0M0 MPUC. Two months after the cystectomy, the patient complained of constipation and painful defecation due to local recurrence and rectal invasion. While colostomy was performed to improve defecation 3 months after cystectomy, he did not receive any chemotherapy due to his progressively worsening general condition. Six months after cystectomy, he died following rapid metastases. Our findings, in this case, confirm that bladder cancer in HD patients tends to be pathologically more advanced. Therefore, regular screening is recommended for its early detection in HD patients.

Selective E to Z isomerization of 1,3-Dienes Enabled by A Dinuclear Mechanism.

The E/Z stereocontrol in a C=C bond is a fundamental issue in olefin synthesis. Although the thermodynamically more stable E geometry is readily addressable by thermal Z to E geometric isomerization through equilibrium, it has remained difficult to undergo thermal geometric isomerization to the reverse E to Z direction in a selective manner, because it requires kinetic trapping of Z-isomer with injection of chemical energy. Here we report that a dinuclear PdI-PdI complex mediates selective isomerization of E-1,3-diene to its Z-isomer without photoirradiation, where kinetic trapping is achieved through rational sequences of dinuclear elementary steps. The chemical energy required for the E to Z isomerization can be injected from an organic conjugate reaction through sharing of common Pd species.

Complete response to pembrolizumab in recurrent nested variant of urothelial carcinoma.

INTRODUCTION: The nested variant of urothelial carcinoma is rare and shows poor prognosis. We report a case of complete response to pembrolizumab in recurrent nested variant. CASE PRESENTATION: A 50-year-old man visited another hospital with hematuria and weight loss. Clinical stage T4aN0M0 bladder cancer and acute renal failure were diagnosed. He was referred to our hospital and underwent radical cystectomy. Histological examination showed pathological stage T4aN2 nested variant of urothelial carcinoma. He received 3 cycles of gemcitabine and carboplatin adjuvant chemotherapy. However, para-aortic lymph node metastasis appeared 7 months after cystectomy. He received pembrolizumab as systemic chemotherapy. After 10 cycles, the lesion remained undetectable and we evaluated the response as complete. He has received 18 cycles in total and no recurrences or metastases have been observed. CONCLUSION: Pembrolizumab may offer effective treatment for nested variant of urothelial carcinoma.

Sepsis-associated purpura fulminans caused by emphysematous cystitis.

INTRODUCTION: Emphysematous cystitis is a rare pathology characterized by gas bubbles within the bladder wall and lumen from gas-producing bacteria. Sepsis-associated purpura fulminans is also rare and shows poor clinical outcomes. CASE PRESENTATION: A 73-year-old man was hospitalized at a nearby hospital due to chronic subdural hematoma, symptomatic epilepsy, and diabetes mellitus. He was transferred to our hospital with fever, low blood pressure, and cyanosis of the legs, and was diagnosed with septic shock due to emphysematous cystitis with purpura fulminans. He underwent intensive treatment, including retroperitoneal drainage. Urine culture was positive for Citrobacter freundii. His general condition gradually improved and diffuse air decreased after surgery, but progressive purpuric skin necrosis became evident on the legs, which could not be salvaged. He died on the 25th hospital day. CONCLUSION: Sepsis-associated purpura fulminans caused by emphysematous cystitis shows a very poor prognosis irrespective of intensive treatment, including retroperitoneal drainage.

Increased expression of HMGA1 correlates with tumour invasiveness and proliferation in human pituitary adenomas.

AIMS: High-mobility group A1 (HMGA1) is highly expressed in various benign and malignant tumours. The development of pituitary adenoma in Hmga1 transgenic mice has been reported. However, no studies have investigated HMGA1 expression and its clinical significance in human pituitary adenomas. METHODS AND RESULTS: Immunohistochemical expression of HMGA1 was analysed with respect to various clinicopathological factors in 95 pituitary adenomas. Nuclear expression of HMGA1 was observed in 62% of pituitary adenomas, whereas normal adenohypophysial tissues were negative. Although HMGA1 expression was frequently detected in clinically non-functioning adenomas - 90% of silent adrenocorticotropic hormone (ACTH), 76.2% of follicle-stimulating hormone/luteinizing hormone and 100% of null cell adenomas - it was also detected in 48.1% of growth hormone (GH), 60% of mixed GH/prolactin (PRL), 62.5% of PRL, 66.6% of thyroid-stimulating hormone and 37.5% of ACTH adenomas. HMGA1 expression was significantly higher in invasive adenomas or macroadenomas than in non-invasive adenomas or microadenomas (invasive versus non-invasive, P < 0.05; macroadenoma versus microadenoma, P < 0.05). In addition, HMGA1 showed the highest level in grade IV, more aggressive pituitary adenomas, than in grades I, II and III (IV versus I, P = 0.01; IV versus II, P = 0.01; IV versus III, P = 0.07). Furthermore, a significant correlation between HMGA1 expression and MIB-1 labelling index was observed (R = 0.368, P < 0.0002). CONCLUSIONS: These findings suggest that HMGA1 up-regulation has an important oncogenic role in pituitary tumorigenesis, as well as being a novel molecular marker of tumour proliferation and invasiveness.

[Successful rituximab monotherapy in a patient with mucosa-associated lymphoid tissue lymphoma of the rectum with trisomy 3, 18].

A 62-year-old man was referred to our hospital with enlargement of mucosa-associated lymphoid tissue (MALT) lymphoma of the rectum after the eradication of Helicobacter pylori. The patient was given a diagnosis of stage I MALT. Endoscopic observation revealed an enlarged rectal tumor with 3, 18 double trisomy. Rituximab monotherapy was given and complete remission was achieved. Rituximab monotherapy can be useful for MALT lymphoma of the rectum.

A Long-term Survival Case of Pulmonary Tumor Thrombotic Microangiopathy due to Gastric Cancer Confirmed by the Early Diagnosis based on a Transbronchial Lung Biopsy.

Pulmonary tumor thrombotic microangiopathy (PTTM) is an acute, progressive, and fatal disease. PTTM manifests as subacute respiratory failure with pulmonary hypertension, progressive right-sided heart failure, and sudden death. An antemortem diagnosis of PTTM is very difficult to obtain, and many patients die within several weeks. We herein report a case of PTTM diagnosed based on a transbronchial lung biopsy. In this case, we finally diagnosed PTTM due to gastric cancer because of its histological identity. The patient was administered chemotherapy, including angiogenesis inhibitors, against gastric cancer at an early age and survived for a long time.

Overexpression of HMGA2 relates to reduction of the let-7 and its relationship to clinicopathological features in pituitary adenomas.

High-mobility group A2 is highly expressed during embryogenesis and in various benign and malignant tumors. Recent studies report that high-mobility group A2 is negatively regulated by the let-7 microRNAs (miRNAs) family in vitro. The development of pituitary adenomas in high-mobility group A2 transgenic mice showed that high-mobility group A2 may be involved in pituitary tumorigenesis. However, no studies have investigated the clinical significance of high-mobility group A2 and its relationship to the let-7 miRNA family in human pituitary adenomas. Using immunohistochemistry, we analyzed high-mobility group A2 expression with respect to various clinicopathologic factors in 98 pituitary adenomas. Overexpression of high-mobility group A2 was observed in 39% (38/98) of pituitary adenomas compared with normal adenohypophysial tissue and was frequently found in adenomas including prolactin (PRL), adrenocorticotrophic hormone, or follicle-stimulating hormone/luteinizing hormone and in null cell adenomas, but relatively rare in growth hormone (GH) and mixed GH/PRL adenomas. High-mobility group A2 expression was significantly associated with tumor invasion (P<0.05) and was significantly higher in grade IV than in grades I, II, and III adenomas (P<0.05). High levels of high-mobility group A2 expression were more frequently observed in macroadenomas than in microadenomas (P<0.05). High levels of high-mobility group A2 expression also significantly correlated with the proliferation marker Ki-67 (P<0.0001). Real-time quantitative RT-PCR analysis was carried out to evaluate the expression of let-7 in 55 pituitary adenomas. Subsequently, decreased expression of let-7 was confirmed in 23 of 55 (42%) adenomas and was correlated with high-grade tumors (P<0.05). An inverse correlation between let-7 and high-mobility group A2 expression was evident (R=-0.33, P<0.05). These findings support a causal link between let-7 and high-mobility group A2 whereby loss of let-7 expression induces high-mobility group A2 upregulation that represents an important mechanism in pituitary tumorigenesis and progression.

Intimal sarcoma arising from the common iliac artery presenting with artery occlusion : a case report and literature review.

We present a rare case of intimal sarcoma arising from the common iliac artery in an 82-year-old man who presented with intermittent claudication. He had undergone endovascular therapy with self-expanding stents to both iliac arteries that had occluded soon after placement. After salvage bypass grafting, a diagnosis of intimal sarcoma with angiosarcoma phenotype from the iliac artery was made. Further bypass graft surgery relieved symptoms temporarily. However, the tumor progressed and the left limb became ischemic. The chemotherapy of eribulin did not prevent tumor progression. The patient died of the disease 20 months after the first surgery. J. Med. Invest. 66 : 205-208, February, 2019.