[Cancer of the Ascending Colon Diagnosed at the Same Time as Breast Cancer Following Leukemia Treatment for Which Laparoscopic Surgery Was Performed-A Case Report].

An 83-year-old woman received 8 courses of chemotherapy(mogamulizumab)for adult T cell leukemia in the hematolo- gy department of our hospital, after which she achieved complete remission and was followed up with chemotherapy(VP/ MST: sobuzoxane/etoposide)as an outpatient. Later, diarrheal symptoms appeared, and detailed examinations led to a diagnosis of cancer of the ascending colon. Although no distal metastasis was found, breast cancer was also revealed in the C area of the right breast. The general status of the patient was favorable; thus, right pectoral muscle-conserving mastectomy and concomitant sentinel lymph node biopsy were performed through laparoscope-assisted extended right hemicolectomy. The postoperative course was favorable, and she was discharged on hospital day 7. The excised tumors were pathologically diagnosed as stageⅠ breast cancer and stage Ⅲa colorectal cancer. Chemotherapy(VP/MST)was administered without adjuvant chemotherapy. Presently, 18 months after surgery, complete remission of adult T cell leukemia has been maintained, without metastasis and recurrence of cancer of the ascending colon and breast cancer.

Primary central chondrosarcoma of long bone, limb girdle and trunk: Analysis of 174 cases by numerical scoring on histology.

The aims of this study were: (i) to elucidate clinicopathological characteristics of pcCHS of long bones (L), limb girdles (LG) and trunk (T) in Japan; (ii) to investigate predictive pathological findings for outcome of pcCHS of L, LG and T, objectively; and (iii) to elucidate a discrepancy of grade between biopsy and resected specimens. Clinicopathological profiles of 174 pcCHS (79 male, 95 female), of L, LG, and T were retrieved. For each case, a numerical score was given to 18 pathological findings. The average age was 50.5 years (15-80 years). Frequently involved sites were femur, humerus, pelvis and rib. The 5-year and 10-year disease-specific survival (DSS) rates [follow-up: 1-258 months (average 65.5)] were 87.0% and 80.4%, respectively. By Cox hazards analysis on pathological findings, age, sex and location, histologically higher grade and older age were unfavorable predictors, and calcification was a favorable predictor in DSS. The histological grade of resected specimen was higher than that of biopsy in 37.7% (26/69 cases). In conclusion, higher histological grade and older age were predictors for poor, but calcification was for good prognosis. Because there was a discrepancy in grade between biopsy and resected specimens, comprehensive evaluation is necessary before definitive operation for pcCHS.

Distribution of myofibroblast and tenascin-C in cystic adventitial disease: comparison with ganglion.

Cystic adventitial disease (CAD) is a rare peripheral artery disorder which shows the development of gelatinous cysts in the adventitia. Although several theories for the pathogenesis of CAD have been postulated, the etiology of CAD remains unclear. Histological examination of three CAD cases revealed that these cyst walls were composed of fibrous tissue and lacked both epithelial and endothelial lining. The surfaces of these cysts were partially covered with spindle-shaped cells, similar to the interstitial cells within the cyst wall. A pool of mucinous material in the adventitia was evident. Distribution of vimentin-positive spindle-shaped cells and scattered CD68-positive oval-shaped cells in the cyst wall was revealed by immunohistochemistry. A part of vimentin-positive spindle-shaped cells demonstrated to be positive for α-smooth muscle actin, indicating the presence of myofibroblasts in the cyst wall. A focal tenascin-C-positive area was observed in the cyst wall of our CAD cases. Presence of two different cell types, proliferation of myofibroblasts and expression of tenascin-C were consistent with those of cyst walls of 20 surgically resected ganglions. These results suggest that CAD may arise as capsular synovial structures, similar to ganglion cysts.

Characterization of novel germline c-kit gene mutation, KIT-Tyr553Cys, observed in a family with multiple gastrointestinal stromal tumors.

We found a novel type germline mutation at exon 11 of the c-kit gene, which results in a substitution of Tyr to Cys at codon 553 of the c-kit gene product (KIT-Tyr553Cys), in a 68-year-old female patient with multiple gastrointestinal stromal tumors (GISTs). In the present study, we carried out mutational analysis in her family members to determine the carriers and characterized the mutation by introducing the corresponding mutation (murine KIT-Tyr552Cys) into expression vector possessing murine c-kit cDNA. Mutational analysis of peripheral blood leukocytes of her family members revealed that a 44-year-old son had the same mutation, but at present he had neither apparent symptoms nor images of multiple GISTs. By transfection with the expression vector possessing the murine mutant c-kit cDNA, interleukin-3-dependent Ba/F3 murine lymphoid cells started growing autonomously without any growth factors, indicating that the mutation was considered to be of gain-of-function. Imatinib, a small molecule of tyrosine kinase inhibitor, effectively inhibited autophosphorylation of KIT-Tyr552Cys. Nilotinib, another small molecule of the KIT inhibitor, also effectively inhibited autophosphorylation of KIT-Tyr552Cys. In fact, proliferation of Ba/F3 cells expressing KIT-Tyr552Cys was effectively inhibited by both imatinib and nilotinib. These findings indicate that the novel type human KIT-Tyr553Cys mutation is the cause of the present familial and multiple GISTs, and that both imatinib and nilotinib might effectively inhibit the growth of GISTs developing in the patients of this family.

Synovial sarcoma is a stem cell malignancy.

Synovial sarcoma (SS) is a malignant soft tissue tumor characterized by its unique t(X;18)(p11;q11) chromosomal translocation leading to the formation of the SS18-SSX fusion gene. The resulting fusion protein product is considered to play as an aberrant transcription factor and transform target cells by perturbing their gene expression program. However, the cellular origin of SS is highly debated. We herein established two novel human SS cell lines, named Yamato-SS and Aska-SS, and investigated their biological properties. We found the self-renewal ability of these cells to generate sarcospheres, to form tumors in serial xenotransplantation and reconstitute the tumor phenotypes without fractionation by any surface markers. Both SS cells as well as clinical tissue specimens from 15 patients expressed the marker genes-associated stem cell identity, Oct3/4, Nanog, and Sox2. We also found that both SS cells displayed limited differentiation potentials for mesenchymal lineages into osteocytes and chondrocytes albeit with the expression of early mesenchymal and hematopoietic lineage genes. Upon SS18-SSX silencing with sequence-specific siRNAs, these SS cells exhibited morphological transition from spherical growth in suspension to adherent growth in monolayer, additional expression of later mesenchymal and hematopoietic lineage genes, and broader differentiation potentials into osteocytes, chondrocytes, adipocytes, and macrophages in appropriate differentiation cocktails. Collectively, these data suggest that a human multipotent mesenchymal stem cell can serve as a cell of origin for SS and SS is a stem cell malignancy resulting from dysregulation of self-renewal and differentiation capacities driven by SS18-SSX fusion protein.

Posterior interosseous nerve palsy caused by synovial chondromatosis arising in the annular periradial recesses of the elbow.

We present a rare case report of a patient who presented with posterior interosseous nerve palsy caused by synovial chondromatosis. Synovial chondromatosis arising in the annular periradial recesses of the elbow joint was detected, and the mass developed two major portions constricted with the annular ligament. After surgical resection, posterior interosseous nerve palsy fully recovered and there was no recurrence of the lesion of synovial chondromatosis.

Malignant pleural mesothelioma with heterologous elements.

AIMS: Malignant pleural mesothelioma with heterologous elements (such as osseous, cartilaginous or rhabdomyoblastic differentiation) is very rare. We tried to differentiate such mesothelioma cases from extraskeletal pleural osteosarcoma, which is very challenging. METHODS: We compared 10 malignant pleural mesotheliomas (three biphasic and seven sarcomatoid types) with two pleural osteosarcomas using clinicopathological and immunohistochemical methods, and also fluorescence in situ hybridisation (FISH) to examine for homozygous deletion of p16. RESULTS: The median age was 72 years for mesotheliomas, and 69 years for osteosarcoma. For mesothelioma, eight cases were male and two were female. Growth was diffuse in all mesothelioma cases except case 10, where it was localised, as it was for the two osteosarcomas. Among mesothelioma cases, 80% displayed osteosarcomatous and 60% chondromatous elements, while 10% exhibited rhabdomyoblastic ones. Immunohistochemical labelling for calretinin and AE1/AE3 was present in 8/10 and 7/10 mesotheliomas, respectively, but in only one osteosarcoma. Loss of methylthioadenosine phosphorylase was seen in 5/7 mesotheliomas. FISH analysis revealed homozygous deletion of p16 in 5/8 mesothelioma and 2/2 osteosarcoma. Median survival was 6.5 months after biopsy or surgical operation in mesothelioma, and 12 months after operation in osteosarcoma. CONCLUSIONS: Although median survival was longer for osteosarcoma than for malignant mesothelioma, we could not differentiate mesothelioma from pleural osteosarcoma on the combined basis of clinicopathological and immunohistochemical data, and FISH analysis. However, diffuse growth was more frequent in mesothelioma than in osteosarcoma.

Diffuse Alveolar Septal Amyloidosis With Wild-Type Transthyretin With Spontaneous Lung Hematoma.

We experienced a mass formation in the right lower lobe in a patient with cardiac amyloidosis and heart failure. Radiologic findings of the chest showed no abnormality except a mass. The patient had non-valvular atrial fibrillation and was taking edoxaban. Surgical resection of the mass revealed a hematoma. Further pathologic evaluation revealed diffuse alveolar septal amyloidosis with transthyretin (ATTR). The genetic testing found no mutation in the TTR gene. Therefore, systemic wild-type TTR amyloidosis (ATTRwt) was confirmed. Alveolar septal ATTRwt is rare and patient had alveolar septal ATTRwt with spontaneous lung hematoma.

Expression of p16 in nodular fasciitis: an implication for self-limited and inflammatory nature of the lesion.

Nodular fasciitis (NF) is a self-limited tumorous lesion occurring in the upper as well as lower extremities. NF is composed of a proliferation of "primary culture"-like myofibroblastic cells with nuclear atypia and large nucleoli, thus mimicking sarcoma. NF harbors a promoter-swapping fusion gene containing the entire coding region of USP6 gene. Therefore, NF is a tumor with a fusion oncogene but self-limited. In order to explore why NF is self-limited, we examined whether myofibroblastic cells in NF express p16 protein, a gene product of CDKN2A gene and an inhibitor of cyclin-dependent kinase 4 (CDK4) as well as one of the hallmarks of cellular senescence. We immunohistochemically demonstrated strong and diffuse expression of p16 in myofibroblastic cells in 11 out of 15 cases of NF, and strong but partial expression in the remaining 4 of the cases. We also showed that 15 out of 15 cases of NF were immunohistochemically negative or only showed focal and faint immunopositivity for CDK4, murine double minute 2 (MDM2), and TP53 proteins. Furthermore, there were no significant changes in the copy number of CDKN2A, CDK4 and MDM2 genes, and no significant mutations in TP53, RB1, and CDKN2A genes in 1 case of NF selected. These data suggest a possible involvement in cell cycle arrest and presumed cellular senescence by p16 in myofibroblastic cells in NF. This may explain the self-limited as well as inflammatory nature of NF as a senescence-associated secretory phenotype.

[PRIMARY SQUAMOUS CELL CARCINOMA OF THE PROSTATE: A CASE REPORT].

SQUAMOUS CELL CARCINOMA, prostate carcinoma, The patient was a 67-year-old man who visited our hospital with urge incontinence. His serum prostatic specific antigen level was normal (1.191 ng/mL). Digital rectal examination and magnetic resonance imaging suggested common prostatic carcinoma. A transperineal needle biopsy was performed, and the histological diagnosis was squamous cell carcinoma (SCC). The serum SCC-antigen level was normal, and the patient underwent a radical prostatectomy. Computed tomography 15 months later revealed multiple metastases in the lymph nodes. The patient underwent systemic chemotherapy using fluorouracil (5-FU) and cisplatin (CDDP). After 3 courses of chemotherapy, the multiple lymph node metastases could not be detected.

Quantitative evaluation of carotid plaque echogenicity by integrated backscatter analysis: correlation with symptomatic history and histologic findings.

BACKGROUND AND PURPOSE: Echogenicity of carotid plaque well reflects the risk of ischemic stroke and may be predictive of the histologic content of the plaque. However, objective evaluation of plaque echogenicity has been hampered by a lack of established quantitative measures. This study examined the relation between echogenicity assessed by integrated backscatter (IBS) analysis and (1) symptomatic history and (2) histologic features of carotid plaques. METHODS: We used acoustic densitometry to quantify by IBS analysis the echogenicity of 31 carotid plaques of 26 patients undergoing carotid endarterectomy or stenting. IBS was subsequently compared with histologic findings of the respective tissue in 10 patients who underwent endarterectomy. The IBS value was calibrated with 2 reference structures (vessel lumen and adventitia) as the IBS index. RESULTS: The IBS index of symptomatic plaques was lower than that of asymptomatic plaques (23.1 +/- 12.5 vs. 36.5 +/- 18.2, p < 0.05). The IBS index in fatty/necrotic atheromatous sites (n = 20, 16.6 +/- 10.7) was lower than that in fibrous (n = 26, 42.4 +/- 13.6, p < 0.01) or calcified (n = 11, 87.7 +/- 17.4, p < 0.01) sites and the same as that in intraplaque hemorrhagic sites (n = 50, 23.6 +/- 16.9). CONCLUSIONS: Carotid plaque echogenicity, as quantitatively assessed by IBS analysis, correlates well with the presence or absence of prior symptoms and histologic contents of the plaques. IBS analysis may aid in the assessment of carotid plaque-related risk of stroke.

Expression of p21Cip1/Waf1 and p27Kip1 in small cell neuroendocrine carcinoma of the uterine cervix.

Small-cell neuroendocrine carcinoma of the uterine cervix (SCCC), a rare but malignant cervical neoplasm, has a highly aggressive phenotype that requires more intensive treatment than other cervical tumors. Immunohistochemical methods were used to compare the expression of p21Cip1/Waf1 and p27Kip1 in SCCC and squamous cell carcinoma, the most common type of cervical cancer. In SCCC, p21 expression was significantly reduced compared with squamous cell carcinoma, whereas expression of p27 was similar in both carcinomas. Reduced expression of p21 could be a helpful diagnostic marker and may contribute to the invasive phenotype of SCCC.

An extremely rare case of primary malignancy in giant cell tumor of bone, arising in the right femur and harboring H3F3A mutation.

We experienced a case of primary malignancy in giant cell tumor of bone (GCTB), arising in the right femur and harboring H3F3A mutation. A 27-year-old Japanese male without any prior disease history complained of pain in his right hip joint and right lower limb. Radiological images revealed an osteolytic and multicystic lesion existing mainly at the proximal epiphysis of the right femur. Preoperative clinical diagnosis was GCTB, although irregular marginal sclerosis was an atypical radiographic finding for conventional GCTBs. Biopsy sample from the lesion revealed the coexistence of typical GCTB and undifferentiated high-grade round cell sarcoma. Despite of the wide local resection of the tumor with preoperative and postoperative chemotherapy, the patient died of multiple distant metastases of the tumor 9 months after the surgery. Since heterozygous H3F3A c. 103G>T (p. Gly34Trp) mutation was detected not only in the biopsy sample from the primary site with typical GCTB and high-grade sarcoma components but also in the resected material from the metastatic site with only pure high-grade sarcoma component, the tumor was considered originally derived from conventional GCTB and acquire malignant transformation to high-grade sarcoma. Thus, this is an extremely rare case of primary malignancy in GCTB and the first case report of primary malignancy in GCTB proved the presence of H3F3A mutation even in the sarcoma component.

Ectopic adrenocorticotropic hormone syndrome associated with olfactory neuroblastoma: acquirement of adrenocorticotropic hormone expression during disease course as shown by serial immunohistochemistry examinations.

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a condition of endogenous hypercortisolism sustained by an extrapituitary ACTH-secreting tumor. Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the sinonasal tract and is derived from the olfactory epithelium. Because the paranasal sinus is not a common site of EAS, the development of ONB in patients with EAS is rare. We herein report the first known case of ONB with acquirement of ACTH production during the clinical course as proven by immunohistochemistry. A 50-year-old man diagnosed with ONB was referred to our department in July 2015 because of hypokalemia, hyperglycemia, decreased eosinophil and granulocyte counts, and elevated serum levels of ACTH and cortisol. Although two previous ONB biopsy specimens (2011 and 2014) showed no ACTH immunoreactivity, a newly obtained specimen in August 2015 clearly showed ACTH immunoreactivity. This is the first case of ectopic ACTH syndrome associated with an ONB that acquired the ability to express ACTH during its clinical course as shown by serial immunohistochemical examinations.

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model.

Thrombo-occlusive cerebrovascular disease resulting in stroke and permanent neuronal loss is an important cause of morbidity and mortality. Because of the unique properties of cerebral vasculature and the limited reparative capability of neuronal tissue, it has been difficult to devise effective neuroprotective therapies in cerebral ischemia. Our results demonstrate that systemic administration of human cord blood-derived CD34(+) cells to immunocompromised mice subjected to stroke 48 hours earlier induces neovascularization in the ischemic zone and provides a favorable environment for neuronal regeneration. Endogenous neurogenesis, suppressed by an antiangiogenic agent, is accelerated as a result of enhanced migration of neuronal progenitor cells to the damaged area, followed by their maturation and functional recovery. Our data suggest an essential role for CD34(+) cells in promoting directly or indirectly an environment conducive to neovascularization of ischemic brain so that neuronal regeneration can proceed.

Surgical results of lung cancer with sarcoid reaction in regional lymph nodes.

BACKGROUND: There have been few reports of sarcoid reaction in the regional lymph nodes associated with lung cancer. The purpose of this study was to analyze the surgical results of lung cancer with sarcoid reaction. METHODS: Of 1733 lung cancer patients undergoing surgical treatment in our institute from 1990 to 2004, we reviewed 22 patients (1.3%) with sarcoid reaction in the regional lymph nodes of lung cancer. RESULTS: On pre-operative computed tomography (CT), mediastinal lymph node swelling was detected in 19 patients (86%) as clinical N3 disease (c-N3) in six or as c-N2 in 13, while three patients were classified as c-N0. To these 19 patients, lymph node status was histologically checked by mediastinoscopy in four patients, sternotomy approach in two and open mini-thoracotomy in 13. Because the sampling-biopsy nodes showed no tumor metastasis, radical surgery was promptly performed. However, four patients (18%) were finally judged to have pathological lymph node positive disease. Five patients were in pathological stage (p-stage) IA, nine in p-stage IB, five in p-stage IIB, two in p-stage IIIA, and one in stage IIIB. The overall 3-, and 5-year survival rates of these patients were 85.2 and 77.7%, respectively, with no significant difference compared to those of the remaining patients without sarcoid reaction. CONCLUSIONS: Because lung cancer patients with sarcoid reaction in the regional lymph nodes frequently show mediastinal lymph node swelling on CT, radical resection should be performed after confirming the node status by appropriate sampling biopsy. It seems that surgical results of lung cancers with sarcoid reaction in the regional nodes are not prognostically different from those without sarcoid reaction.

Nuclear expression of STAT5 in intraductal papillary mucinous neoplasms of the pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) are noninvasive lesions of the pancreas and classified as intraductal papillary mucinous adenomas (IPMAs), borderline IPMNs, and intraductal papillary mucinous carcinomas (IPMCs). Expression patterns of the specific genes alter during IPMN progression. Based on the evidence that signal transducers and activators of transcription (STAT) 5 play important roles in tumor development, we tested STAT5 expression in IPMAs, borderline IPMNs, and IPMCs by immunohistochemical method. STAT5 frequently expressed in the nuclei of tumor cells of borderline IPMNs or IPMCs but was not observed in those of IPMAs. Nuclear expression of STAT5 protein correlated to the Ki-67 labeling index of the examined IPMNs. STAT5 protein could contribute to the progression and proliferation of IPMNs.

Acute adrenal crisis after orthopedic surgery for pathologic fracture.

BACKGROUND: Adrenal crisis after surgical procedure is a rare but potentially catastrophic life-threatening event. Its manifestations, such as hypotension, tachycardia, hypoxia, and fever mimic the other more common postoperative complications. Clinical outcome is dependent upon early recognition of the condition and proper management with exogenous steroid administration. CASE PRESENTATION: We report a 75-year-old man who presented with shock immediately after surgery for a femoral fracture from lung cancer metastasis. Anemia and severe hyponatremia were detected. Despite adequate fluid resuscitation, nonspecific symptoms including hypotension, tachycardia, hypoxia, fever and confusion occurred. Emergent CT revealed enlarged bilateral adrenal glands. Under the diagnosis of adrenal crisis due to metastatic infiltration of adrenal glands, the patient was treated with appropriate steroid replacement resulting in rapid improvement and recovery. CONCLUSION: We describe a case of adrenal crisis caused by the lack of adrenal reserve based on metastatic involvement and surgical stress, the first published case of adrenal crisis after surgery for a pathologic fracture from lung cancer metastasis. Surgeons treating pathologic fractures should be aware of this complication and familiar with its appropriate therapy because of increasing opportunity to care patients with metastatic bone tumors due to recent advances in cancer treatment.