Pilomatrical carcinosarcoma in the very elderly: A case report.

Pilomatrical carcinosarcomas are very rare tumors. To the best of our knowledge, only nine cases diagnosed with pilomatrical carcinosarcomas have been reported. The present study reported on a case of pilomatrical carcinosarcoma in the posterior part of the left auricle of a 100-year-old male patient. The tumor histologically comprised the following two components: Pilomatrical carcinoma and undifferentiated spindle cell sarcoma. The pilomatrical carcinoma comprised atypical basaloid cells and shadow cells. The basaloid cells had basophilic cytoplasm, clear nucleoli and deeply stained nuclear chromatin. The undifferentiated spindle cell sarcoma comprised atypical spindle cells. Both components contained numerous mitotic cells. The boundary area between the carcinoma and sarcoma smoothly transitioned into each other. The carcinoma cells and a portion of the sarcoma cells were positive for ß-catenin in the cytoplasm with or without the nuclei. These results suggested that the two components developed from the same origin.

A case of high-grade mucinous tubular and spindle cell carcinoma.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare renal cell carcinoma that initially presents as low-grade renal cell carcinoma. However, cases of MTSCC with high-grade histology and poor prognosis have been reported. Here, we report a case of MTSCC with high-grade histological features and metastasis. A 77-year-old woman consulted a hospital following frequent and painful micturition. Computed tomography scan revealed a tumor of the left kidney. First, chemotherapy was performed, with no effects. Therefore, nephrectomy was subsequently performed. Histologically, the tumor showed the features of MTSCC with sarcomatoid component. Metastasis of the tumor into the lymph node was also observed. Although adjuvant chemotherapy was performed after nephrectomy, metastasis to the lungs and bone and local recurrence was observed. The patient is still alive 2 years after nephrectomy with metastasis and recurrence of the tumor. High-grade MTSCC shows a relatively poor prognosis, specifically MTSCC with metastasis upon nephrectomy.

An Autopsy Case of Rupture of Infectious Thoracic Aortitis Induced by Methicillin-Resistant Staphylococcus Aureus.

BACKGROUND Infectious aortitis has a poor prognosis and high mortality rate if untreated. Here, we report a case of rupture of infectious aortitis induced by methicillin-resistant staphylococcus aureus (MRSA). CASE REPORT An 83-year-old female patient was hospitalized due to continuous fever and diarrhea, which was diagnosed as colitis. The colitis was determined to have been induced by small vessel vasculitis upon histological examination. Fasting and central venous hyperalimentation using a peripherally inserted central catheter (PICC) were carried out for rest of the intestine. Swelling and pus were observed at the insertion site of the PICC. Since methicillin resistant staphylococcus aureus (MRSA) was detected in the culture of the pus and the blood, the patient was treated with vancomycin. After confirming that the blood culture became negative, prednisolone (PDL) was started as therapy for the colitis. Her diarrhea and fever improved. After vancomycin was stopped, MRSA-arthritis appeared. She suddenly died due to acute massive hemorrhage into the mediastinum and left thoracic cavity from the atherosclerotic ulcer of the thoracic aorta. It took 98 days from the first detection of MRSA in her blood to her death. We found gram-positive coccus in the ruptured aortic ulcer and we also detected MRSA gene by polymerase chain reaction in the ulcer. These results suggest that MRSA could colonize in the aortic ulcer during the MRSA-bacteremia and the MRSA could contribute to the vulnerability of the aortic wall. CONCLUSIONS After septicemia occurrs in an elderly person, the patient should be followed up by considering infectious aortitis, especially when the patient has several risk factors.

Malignant rhabdoid tumour in an adult kidney: A case report.

Malignant rhabdoid tumours (MRTs) in the kidney are rare paediatric tumours that are extremely rare in adults. We herein report the case of an adult patient with a renal MRT. A 79-year-old Japanese woman was found to have a tumour sized 63×48 mm in the left kidney, in addition to multiple metastatic bone and lymph node lesions. The needle biopsy specimen obtained from the patient's kidney revealed tumour cells with rhabdoid characteristics: The cells appeared large, round or polygonal, with eccentrically located nuclei and prominent nucleoli. Immunohistochemically, the tumour cells were positive for vimentin, epithelial membrane antigen, CAM 5.2, and p53, and negative for INI1, cytokeratin (CK)7, CK20, α-methylacyl-CoA racemase, S100, CD45, renal cell carcinoma marker, anaplastic lymphoma kinase, α-smooth muscle actin, desmin, MyoD, myogenin, human melanoma black 45 and melan A. Therefore, the tumour was diagnosed as an MRT located in the kidney. Although the patient was treated with axitinib, a tyrosine kinase inhibitor, the renal tumour and its metastatic lesions continued to progress, and the number of metastatic lesions increased. The patient succumbed to the disease 5 months after the first hospital visit. The disease progression was rapid, with a poor prognosis, consistently with previous reports that of MRTs in the adult kidney.

Extra-gastrointestinal stromal tumor with a large cyst.

Gastrointestinal stromal tumors (GISTs) arising at sites other than the alimentary tract are rare, and they are called extra-GISTs (EGISTs). We report a case of a large EGIST forming a cyst, probably arising in the mesentery of the transverse colon. A 64-year-old Japanese man presented to a hospital with an abdominal tumor forming a large cyst. Intraoperatively, the tumor was neither present in nor in contact with the alimentary tract. It was present in the mesentery of the transverse colon and was attached to the greater omentum and peritoneum, immediately anterior to the body of the pancreas. The tumor was resected with the spleen and a part of the pancreas. Histological examination of the tumor revealed that it belonged to the high-risk category of cystic EGISTs.

Large-cell neuroendocrine carcinoma arising in the endometrium: A case report.

Large-cell neuroendocrine carcinoma (LCNEC) of the endometrium is an extremely rare, high-grade malignant tumor. We herein report a case of a rapidly growing LCNEC arising in the endometrium. A 52-year-old woman was referred to Toyooka Hospital (Tooyoka, Japan) due to genital bleeding in February 2016. There had been no abnormalities on a regular gynecological and physical examination 3 months prior to the consultation. Imaging (computed tomography and magnetic resonance imaging) and a pelvic examination revealed a tumor sized 16.9×8.4×7.8 mm occupying the intrauterine cavity and extending into the vaginal cavity. Multiple metastatic pelvic and paraaortic lymph nodes were also identified. Continuous bleeding from the tumor was observed, and a blood examination revealed anemia, which was likely due to that bleeding. Biopsy of the tumor was performed, and large atypical cells were identified. The tumor cells were negative for cytokeratin AE1/AE3 and chromogranin A, but positive for CD56 and synaptophysin. There was also an abundance of Ki-67-positive cells in the tumor, altogether suggesting that the tumor was an LCNEC. The patient succumbed to the disease 36 days after the first consultation. Based on the findings of the present case and previously published cases, LCNECs arising in the endometrium may progress rapidly and are associated with an unfavourable outcome. LCNEC should be included in the differential diagnosis in cases of rapidly growing tumors of the uterine corpus.

Mucinous tubular and spindle cell carcinoma with a high nuclear grade and micropapillary pattern: A case report.

Mucinous tubular and spindle cell carcinoma (MTSCC) is rare in renal cell carcinoma (RCC) and usually demonstrates a low nuclear grade and a better prognosis compared with other RCCs. The authors present a case report of MTSCC containing an area of Fuhrman nuclear grade 3, in addition to an area with a micropapillary pattern. An 82-year-old man consulted a hospital due to macrohematuria, and a tumor in the right kidney was detected. The tumor was resected and histologically examined. The tumor consisted of various growth patterns: Elongated tubular structure, a papillary structure containing a micropapillary pattern and solid pattern with spindle cells. The tumor cells demonstrated Fuhrman nuclear grades 2 and 3. Invasion into the lymph vessel and metastasis into the regional lymph node were observed. Thus, the tumor was diagnosed as a high grade MTSCC. Five months following resection, a computed tomography scan suggested metastasis of the tumor into the para-aortic lymph nodes and liver, and the patient succumbed to brain metastasis. When MTSCC of kidney is observed, careful histological observation is important to avoid missing a high nuclear grade area.

Hepatic epithelioid hemangioendothelioma with metastasis to the mesentery of the small intestine: A case report.

Epithelioid hemangioendothelioma (EHAE) is a vascular tumor which, due to its rarity, is often misdiagnosed as other hepatic tumors based on radiological characteristics. We herein report a case of EHAE in the liver and the mesentery of the small intestine. A 64-year-old asymptomatic woman was admitted to the hospital due to a hepatic tumor identified using computed tomography (CT). An enhanced CT scan revealed multiple tumors in the liver and a tumor in the mesentery. One of the hepatic tumors and the mesenteric tumor were resected and histologically examined. The two tumors exhibited similar histological characteristics and were diagnosed as EHAE. When multiple tumors are found in the liver, EHAE should be included in the differential diagnosis, as the prognosis of EHAE differs from that of carcinoma or benign tumors.

Neuroendocrine carcinoma of the lung expressing anaplastic lymphoma kinase on high-sensitivity immunohistochemistry: A case report.

It has been reported that anaplastic lymphoma kinase (ALK) protein is expressed in a proportion of non-small-cell carcinomas (mainly adenocarcinomas). By contrast, high-sensitivity immunohistochemistry (IHC) rarely detects ALK protein expression in neuroendocrine carcinomas (NECs) of the lung, which include small-cell carcinomas and large-cell neuroendocrine carcinomas (LCNECs). We herein present a case of NEC that was identified as ALK-positive via high-sensitivity IHC. A 51-year-old man was diagnosed with small-cell carcinoma in the upper lobe of the right lung. Although high-sensitivity IHC revealed that the tumor weakly expressed the ALK protein, no fusion gene with ALK was found using fluorescence in situ hybridization (FISH). Standard chemotherapy was administered to the patient. Six months after the first visit to the hospital for the tumor, another tumor was identified in the upper lobe of the left lung. The tumor was resected and diagnosed as NEC displaying LCNEC-like characteristics. This NEC also moderately expressed ALK protein by high-sensitivity IHC, without exhibiting fusion genes with ALK on FISH. These data suggest that the presence of ALK fusion genes should be confirmed by FISH or reverse transcription polymerase chain reaction, even if high-sensitivity IHC for ALK protein is positive in lung cancer.

Nivolumab infusion reaction manifesting as plantar erythema and pulmonary infiltrate in a lung cancer patient.

Infusion reaction is an adverse event of therapeutic monoclonal antibodies. Nivolumab, an anti-programmed death-1 antibody, directly activates T cells, which could probably interact with endothelial cells. The etiology of infusion reaction induced by nivolumab may differ from that of other antibodies; however, the detailed clinical features are unknown. We report a case of lung cancer treated with nivolumab, in which the infusion reaction manifested as plantar erythema, followed by a transient local pulmonary infiltrate around the tumor. Physicians should be aware that an infusion reaction induced by anti-programmed death-1 antibodies could appear as local cutaneous and pulmonary adverse events.

Nephrogenic adenoma in elderly patients: Three case reports.

Nephrogenic adenoma (NA), referred to as nephrogenic metaplasia, is a rare benign lesion of the urinary tract. NA is histologically characterized by tubular and papillary formations lined by low cuboidal to columnar epithelial cells. NA is also immunohistochemically characterized by positivity for paired box (PAX) 2, PAX8 and cytokeratin 7, and negative for p63 and prostate-specific antigen. In this study, we present 3 cases of NA arising in the urinary bladder of elderly male patients with predisposing factors: patient 1 had undergone transurethral lithotripsy due to a ureteral stone; patient 2 had undergone transurethral resection of a urothelial carcinoma in the urinary bladder; and patient 3 had been treated with Bacillus-Calmettle-Guérin due to a urothelial carcinoma in the urinary bladder. The characteristics of the NAs of our 3 cases were histologically and immunohistologically consistent with previously reported cases, although 1 patient exhibited a pseudoinvasive pattern. Since NA is a tumor-like benign lesion, it should be clearly differentiated morphologically and immunohistologically from other tumors arising in the urinary tract and from invasion by prostate cancer.

Carcinosarcoma of the uterus: A case report.

Carcinosarcoma is a rare malignant tumor of the uterus with a poor prognosis. We herein present a case of uterine carcinosarcoma in a 67-year-old woman suffering from pervaginal bleeding for 3 months, with progressive anemia. Upon biopsy of the endometrium, the tumor was diagnosed as endometrioid adenocarcinoma. Total hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection were performed. The histological examination revealed that the tumor consisted of serous adenocarcinoma and sarcoma of homologous components. After the operation, chemotherapy with paclitaxel and carboplatin was administered. At approximately 3 years postoperatively, the patient remains alive and recurrence-free.

Immune Dysfunction Associated with Abnormal Bone Marrow-Derived Mesenchymal Stroma Cells in Senescence Accelerated Mice.

Senescence accelerated mice (SAM) are a group of mice that show aging-related diseases, and SAM prone 10 (SAMP10) show spontaneous brain atrophy and defects in learning and memory. Our previous report showed that the thymus and the percentage of T lymphocytes are abnormal in the SAMP10, but it was unclear whether the bone marrow-derived mesenchymal stroma cells (BMMSCs) were abnormal, and whether they played an important role in regenerative medicine. We thus compared BMMSCs from SAMP10 and their control, SAM-resistant (SAMR1), in terms of cell cycle, oxidative stress, and the expression of PI3K and mitogen-activated protein kinase (MAPK). Our cell cycle analysis showed that cell cycle arrest occurred in the G0/G1 phase in the SAMP10. We also found increased reactive oxygen stress and decreased PI3K and MAPK on the BMMSCs. These results suggested the BMMSCs were abnormal in SAMP10, and that this might be related to the immune system dysfunction in these mice.

Increased recruitment of bone marrow-derived cells into the brain associated with altered brain cytokine profile in senescence-accelerated mice.

Bone marrow-derived cells enter the brain in a non-inflammatory condition through the attachments of choroid plexus and differentiate into ramified myeloid cells. Neurodegenerative conditions may be associated with altered immune-brain interaction. The senescence-accelerated mouse prone 10 (SAMP10) undergoes earlier onset neurodegeneration than C57BL/6 (B6) strain. We hypothesized that the dynamics of immune cells migrating from the bone marrow to the brain is perturbed in SAMP10 mice. We created 4 groups of radiation chimeras by intra-bone marrow-bone marrow transplantation using 2-month-old (2 mo) and 10 mo SAMP10 and B6 mice as recipients with GFP transgenic B6 mice as donors, and analyzed histologically 4 months later. In the [B6 → 10 mo SAMP10] chimeras, more ramified marrow-derived cells populated a larger number of discrete brain regions than the other chimeras, especially in the diencephalon. Multiplex cytokine assays of the diencephalon prepared from non-treated 3 mo and 12 mo SAMP10 and B6 mice revealed that 12 mo SAMP10 mice exhibited higher tissue concentrations of CXCL1, CCL11, G-CSF, CXCL10 and IL-6 than the other groups. Immunohistologically, choroid plexus epithelium and ependyma produced CXCL1, while astrocytic processes in the attachments of choroid plexus expressed CCL11 and G-CSF. The median eminence produced CXCL10, hypothalamic neurons G-CSF and tanycytes CCL11 and G-CSF. These brain cytokine profile changes in 12 mo SAMP10 mice were likely to contribute to acceleration of the dynamics of marrow-derived cells to the diencephalon. Further studies on the functions of ramified marrow-derived myeloid cells would enhance our understanding of the brain-bone marrow interaction.

The role of CD5 expression in thymic carcinoma: possible mechanism for interaction with CD5+ lymphoid stroma (microenvironment).

AIMS: Most thymic carcinomas express the lymphocyte marker CD5 aberrantly. This study was performed to examine the role of the self-reactive CD5 antigen in thymic carcinoma. METHODS AND RESULTS: We examined CD5 expression in thymic carcinoma in relation to the lymphoid stroma. All cases of thymic carcinoma examined expressed CD5. A number of CD5(+) lymphocytes were also present in the stroma of thymic carcinoma. The CD5(+) tumour areas were predominantly in contact with the lymphoid stroma, and the expression level was significantly lower in tumour cells than lymphocytes. Although p53 and Bcl-2 expression levels were significantly higher in thymic carcinoma than normal thymic epithelial cells (TECs), they did not differ between CD5(+) and CD5(-) areas. E-cadherin expression in thymic carcinoma was comparable with that of normal TECs, and it also did not differ between these areas. In contrast, both Ki-67 index and mitotic activity were significantly higher in thymic carcinoma than normal TECs, and they were significantly higher in CD5(+) than CD5(-) areas. CONCLUSIONS: CD5 may be induced by interaction with CD5(+) lymphoid stroma, and may be related to tumour proliferation. CD5 induction may also be a significant and/or specific effect of the tumour microenvironment of the thymus.

A case of CD10-negative angioimmunoblastic T cell lymphoma with leukemic change and increased plasma cells mimicking plasma cell leukemia: A case report.

Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell lymphoma, known to express CD3 and CD4, and, frequently, also CD10 and c-Maf-1. Hypergammaglobulinemia is not particularly rare in patients with AITL. However, AITL in conjunction with plasmacytosis in the peripheral blood is rare. The current report presents a case of CD10-negative AITL demonstrating leukemic change and plasmacytosis in the peripheral blood mimicking plasma cell leukemia. A 78-year-old male was admitted to hospital due to systemic lymph node enlargement, high serum IgG and IgA, and increased counts of plasmacytoid cells and lymphoid cells with atypical nuclei in the peripheral blood. Initially, plasma cell leukemia was suspected, due to the extreme increase in the number of plasma cells in the peripheral blood. However, the plasma cells did not show clonal expansion on examination by flow cytometry. Based on histological analyses, following a biopsy of an enlarged lymph node, the patient was diagnosed with AITL. This case suggests that when hypergammaglobulinemia and increases in B-lineage cells are observed, AITL should be considered in addition to disorders of B-lineage cells.

Stem Cell Replacement Improves Expression of SMP30 in db/db Mice.

We have previously reported that replacing bone marrow stem cells may improve hyperglycemia and oxidative stress in db/db mice, a type 2 diabetic mouse model. Senescence marker protein 30 (SMP30) is an antioxidant protein that decreases with aging. However, it has not been clear whether SMP30 decreases in the livers of obese mice, and whether stem cell replacement would improve SMP30 expression in the liver. Bone marrow stem cells of db/db mice were replaced with the bone marrow stem cells of C57BL/6 mice. Plasma cytokine and insulin levels were measured, and glycogen content, expression of SMP30, and fibrosis in the liver were assessed. Our results showed that stem cell replacement increased the expression of SMP30 in the liver, resulting from decreased plasma inflammation cytokines and hyperinsulinemia in db/db mice. This is the first report that stem cell replacement increased the expression of SMP30 in the liver, and may help prevent fibrosis in the liver of db/db mice.

A nuclear factor-κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates GVHD in allogeneic bone marrow transplantation.

GVHD is a crucial mortality factor in allogeneic bone marrow transplantation (ABMT). In this paper, we show that dehydroxymethylepoxyquinomicin (DHMEQ), a novel inhibitor of nuclear factor-κB, suppresses GVHD, resulting in an improved mortality rate in a mouse ABMT model. Bone marrow cells from C57BL/6 mice (B6 mice) were transplanted into lethally irradiated BALB/c mice. Two weeks later, spleen cells from B6 mice were transplanted into the irradiated BALB/c mice. From one week after the injection of spleen cells, when the mice started to show GVHD, the mice were also injected intraperitoneally daily with DHMEQ or vehicle only (DMSO) for 4 weeks. By 80 days after the ABMT, 6/14 of the vehicle-injected mice (43%) had died because of GVHD, whereas all DHMEQ-injected mice survived this observation period and developed milder GVHD than the vehicle-injected mice. When regulatory T cells were reduced by the injection of anti-folate receptor 4 (FR4) antibody, the effects of DHMEQ were reduced. These findings suggest that administration of DHMEQ could become a new strategy for preventing fatalities from GVHD.