Biphasic low-grade nasopharyngeal papillary adenocarcinoma: a case report and literature review.

BACKGROUND: Low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is distinctly rare. We report a patient with a uniquely biphasic LGNPPA; additionally, we review similar tumors reported in the literature. CASE PRESENTATION: A 56-year-old man presented with an asymptomatic pedunculated tumor in the vault of the nasopharynx, at the junction of the nasal septum and the roof, which was discovered during screening for laryngeal cancer. To obtain a definitive diagnosis, the patient underwent endoscopic endonasal surgery under general anesthesia. Immunohistochemical analysis of the tumor revealed it to be an LGNPPA with a prominent spindle cell component. CONCLUSION: To our knowledge, this is the fourth reported LGNPPA exhibiting a spindle cell component and the second with a prominent pathological condition. The prognosis of LGNPPA is usually excellent. Therefore, it is important for clinicians to scrutinize the lesion's pathology to avoid unnecessary, disfiguring surgery.

Primary malignant melanoma of the esophagus successfully treated with nivolumab: a case report.

INTRODUCTION: Primary malignant melanoma of the esophagus is a rare and aggressive disease that tends to have a poor response to chemotherapies. Previous studies have indicated that currently available treatment for primary malignant melanoma of the esophagus is insufficient. Here, we describe a case of recurrent primary malignant melanoma of the esophagus successfully treated with the immune checkpoint inhibitor nivolumab. CASE PRESENTATION: An 81-year-old Japanese female presented with a 3-month history of dysphagia. She was medicated for hypertension and sarcoidosis. The patient had no past history of cutaneous, ocular, or other-site melanomas. An esophagoscopy identified a 30-mm giant tumor in the lower esophagus, at a site 30 cm from the incisors. Enhanced computed tomography revealed wall thickening measuring 30 mm in size at the middle-third of the intrathoracic esophagus, with no significant lymph node infiltration or distant metastasis. Esophageal biopsy showed proliferation of large round tumor cells and melanophages. On the basis of these findings, the patient was diagnosed with esophageal malignant melanoma and underwent esophagectomy and lymph node dissection with gastric tube reconstruction. Although the pathological diagnosis was primary malignant melanoma of the esophagus, the patient presented with multiple lymph node and bone metastases 4 months after surgery. Subsequently, treatment with nivolumab 240 mg every 2 weeks was administered as the first-line treatment. Diffusion-weighted imaging with background body signal suppression following eight courses of nivolumab revealed that the multiple lymph node and bone metastases were markedly reduced. The patient received 30 courses of nivolumab and has maintained the partial response. No severe adverse events related to the immunotherapy were recorded. CONCLUSION: The current study suggests that nivolumab may be a viable option for patients with metastatic primary malignant melanoma of the esophagus. Additional evidence from future clinical trials and research is necessary to fully validate these findings.

Where does the antigen of cutaneous sarcoidosis come from?

BACKGROUND: The antigen pathway of cutaneous sarcoidosis remains obscure. We have investigated topographic involvement of inflammatory cells and lymphatic vessels. METHODS: Eleven cutaneous biopsies from eight patients were studied, along with controls from other granulomatous disorders and various skin lesions. Markers for lymphocytes, dendritic cells (DCs), and lymphatic vessel endothelial cells were detected using immunohistochemistry. RESULTS: S100(+) and CD1a(+) immature DCs (Langerhans cells) occurred more frequently within the epidermis, whereas S100(+), fascin(+), or CD83(+) maturing DCs occurred more frequently beneath the epithelium in cutaneous sarcoidosis cases than in controls (e.g. CD83, cutaneous sarcoidosis vs. other granulomatous disorders: r = 0.557, p = 0.011). Fascin(+) and CD83(+) mature DCs were often closely attached to CD3(+) T-lymphocytes around dermal granulomas. D2-40(+) lymphatic vessels were often found surrounding dermal granulomas, especially those located in the deeper dermis, in contrast to fascin(+) blood vessels. CONCLUSIONS: Antigen-capturing by immature DCs seems to take place initially in the epidermis, followed by maturation of DCs. These mature DCs may present the processed antigen to T-lymphocytes that cause dermal granulomas either in the interstitium of the upper dermis, or in or around lymphatic vessels of the lower dermis. Environmental antigen could be verified by skin test.

Novel germ line mutation p53-P177R in adult adrenocortical carcinoma producing neuron-specific enolase as a possible marker.

Adrenocortical cancer (ACC) is a rare and aggressive endocrine tumor. The patient presented with a large retroperitoneum tumor and lung metastases. Removal of the adrenocortical tumor with part of the transverse colon and tail of the pancreas, spleen and kidney was successfully performed following chemotherapy. Levels of serum neuron-specific enolase (NSE) were found to be markedly high before surgery and may be clinically useful markers for monitoring tumor status during management. Immunohistochemical studies showed that the cancer cells were positive for NSE and overexpression of p53. We identified a novel germ line variant of the 177 mutant (Pro to Arg; P177R) of p53 by genomic sequencing. The genetic and biochemical data presented in this case confirm the importance of screening for p53 status in ACC with inherited cancer syndrome.

Adenocarcinoma of small intestinal type in retroperitoneal mature teratoma.

We report a case of small intestinal type adenocarcinoma arising in retroperitoneal mature cystic teratoma in a young male. The patient initially experienced intermittent abdominal pain, and radiographic workup revealed an encapsulated retroperitoneal mass. A laparotomy was performed and the resected specimen represented a cystic lesion, the inner surface of which was mostly covered by sebaceous debris with hairs. Microscopically, mature derivatives of all three germ layers as well as completely developed gastrointestinal tract were identified. Adenocarcinoma without stromal invasion was observed adjacent to the small intestinal mucosa. Immunohistochemistry of the adenocarcinoma tissue revealed p53 overexpression and high Ki-67 labeling index as well as positive staining for CD10, cytokeratin 7, and cytokeratin 20. Therefore, the diagnosis of small intestinal adenocarcinoma was made. To our knowledge, this is the first case of small intestinal adenocarcinoma arising in retroperitoneal mature cystic teratoma. A unique feature of this case is that malignant transformation in retroperitoneal mature teratoma arose even in the fully developed intestine. Favorable prognosis due to detection in the 'early stage' is also discussed.

Comparison of serum HER2/neu with immunohistochemical HER2/neu expression for the prediction of biochemical progression in metastatic prostate cancer.

OBJECTIVES: To examine whether pretreatment serum human epidermal growth factor receptor 2 (HER2/neu) and immunohistochemical HER2/neu expression predict biochemical recurrence-free survival in advanced prostate cancer. METHODS: We studied 75 untreated patients with metastatic prostate cancer and compared them to a control group of 97 patients without histologically diagnosed prostate cancer. Serum samples were collected for HER2/neu protein analysis before the patients started endocrine therapy. HER2/neu expression in the prostate tissue was evaluated using immunohistochemical analysis. RESULTS: Serum concentration of HER2/neu in patients with prostate cancer was significantly higher than in those without cancer (P = 0.005). Based on the median HER2/neu value, a cut-off level of 12.5 ng/mL was established to separate low from high serum HER2/neu levels. The biochemical recurrence-free survival rate was significantly lower in patients with a high serum HER2 level (P < 0.001). HER2/neu overexpression was found in 18 patients (24%) by immunohistochemical analysis. Biochemical recurrence-free survival rates did not show a statistically significant difference between HER2/neu positive and negative groups. Multivariate analysis showed that the pretreatment serum HER2/neu value was an independent predictor of biochemical recurrence (P = 0.02). CONCLUSIONS: Pretreatment serum HER2/neu may represent a more valuable tool than immunohistochemical HER2/neu expression for the prediction of biochemical recurrence in metastatic prostate cancer patients.

Primary extraskeletal osteosarcoma of the mesentery: A case report.

INTRODUCTION: Extraskeletal osteosarcoma is a rare malignant soft tissue tumor without attachment to the bone. To the best of our knowledge, we present here the first report of a primary extraskeletal osteosarcoma of the mesentery in Japan. CASE PRESENTATION: A 46-year-old female underwent a health examination, with no complaint. Following an ultrasonography a solid mass was detected in the abdominal cavity. Computed tomography showed a 38 × 25 mm heterogeneously enhancing mass. The latter was characterized by the presence of mottled calcifications and a cystic portion. The tumor was resected with a single incisional laparoscopic curative resection. Histopathological examination revealed the presence of a primary extraskeletal osteosarcoma arising from the mesentery. Postoperative course was uneventful. The patient did not receive chemotherapy during follow-up. She was recurrence free 10 months post-surgery. DISCUSSION: Patients with extraskeletal osteosarcoma generally have a poor prognosis. A tumor size <5 cm represents an important prognostic factor. Unexpectedly, our case was detected by ultrasonography at an early stage. This is the first report of a single incisional laparoscopic resection. CONCLUSION: A primary extraskeletal osteosarcoma of the mesentery is an extremely rare occurrence. Its diagnosis should be taken into consideration also when a soft tissue mass of the mesentery is found.

Tyk2 expression and its signaling enhances the invasiveness of prostate cancer cells.

Protein tyrosine kinase plays a central role in the proliferation and differentiation of various types of cells. One of these protein kinases, Tyk2, a member of the Jak family kinases, is known to play important roles in receptor signal transduction by interferons, interleukins, growth factors, and other hormones. In the present study, we investigated Tyk2 expression and its role in the growth and invasiveness of human prostate cancer cells. We used a small interfering RNA targeting Tyk2 and an inhibitor of Tyk2, tyrphostin A1, to suppress the expression and signaling of Tyk2 in prostate cancer cells. We detected mRNAs for Jak family kinases in prostate cancer cell lines by RT-PCR and Tyk2 protein in human prostate cancer specimens by immunohistochemistry. Inhibition of Tyk2 signaling resulted in attenuation of the urokinase-type plasminogen activator-enhanced invasiveness of prostate cancer cells in vitro without affecting the cellular growth rate. These results suggest that Tyk2 signaling in prostate cancer cells facilitate invasion of these cells, and interference with this signaling may be a potential therapeutic pathway.

DNA damage response in prostate cancer cells after high-intensity focused ultrasound (HIFU) treatment.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a new modality that can be used for local tumor ablation therapy. In the present study, the expression of human checkpoint kinase2 (Chk2), which may have significant roles in the response to DNA damage after HIFU treatment for prostate cancer, was examined. MATERIALS AND METHODS: By immunohistochemistry, the Chk2 expression in human prostate cancer tissues was examined before and after HIFU treatment. The phosphorylation of ataxia-telangiectasia-mutated kinase (ATM), histone H2A variant (H2AX), Chk2 and p53, and the number of apoptotic cells in human prostate cancer cell lines after heat treatment was checked. RESULTS: The expression level of phosphorylated Chk2 was found to be increased after HIFU treatment. In addition, heat treatment induced the phosphorylation of Chk2 proteins examined and led to apoptosis in the prostate cancer cells. CONCLUSION: Our results suggest that DNA double-strand break formation is a possible pathway of HIFU treatment and leads to heat-induced cell killing.

Clinical efficacy of proton magnetic resonance spectroscopy (1H-MRS) in the diagnosis of localized prostate cancer.

BACKGROUND: The objective of this study was to evaluate the efficacy of proton magnetic resonance spectroscopy (1H-MRS) in the detection of prostate cancer. MATERIALS AND METHODS: The experimental group consisted of 20 patients with localized prostate cancer who underwent radical prostatectomy. The sensitivity, positive predictive value and accuracy of the detection of prostate cancer in the 12 sections of the peripheral zone were calculated for prostate biopsy alone, 1H-MRS alone and the combination of these methods, respectively. RESULTS: The sensitivity, the positive predictive value, and the accuracy of the preoperative diagnosis of prostate cancer were 43.7%, 68.9% and 54.6%, respectively, with prostate biopsy alone; 60.6%, 87.8% and 71.4% with 1H-MRS alone; and 88.7%, 88.7% and 87.4% with the combination of biopsy and 1H-MRS, respectively. Combined use of biopsy and 1H-MRS significantly improved the sensitivity, positive predictive value and accuracy of the diagnosis. CONCLUSION: 1H-MRS together with biopsy might improve the diagnostic accuracy in prostate cancer.

Serum level of macrophage colony-stimulating factor is increased in prostate cancer patients with bone metastasis.

Recent evaluation of human prostate tissues has shown predominantly high expression of the macrophage colony-stimulating factor receptor in prostatic intra-epithelial neoplasia or prostate cancer. However, the expression of its ligand, the macrophage colony-stimulating factor (M-CSF), and the biological role of this signaling in prostate cancer has not been analyzed. In this research we determined the relationship of serum M-CSF level to clinical parameters of prostate cancer progression. We measured the serum level of M-CSF in 170 patients with histologically confirmed prostatic adenocarcinoma and in 54 patients in whom prostate cancer was not detected. We also investigated the M-CSF expression in prostate cancer tissues by immunohistochemistry. The serum levels of M-CSF in bone metastatic prostate cancer patients was significantly higher than those in non-metastatic patients, while M-CSF did not differ with regards to histological grade, Gleason score or local tumor progression. M-CSF expression was detected in prostate cancer cells themselves by immunohistochemistry. These results suggest that M-CSF may have a functional role in prostate cancer progression.

Multiple aortic aneurysms complicated by a rupture in the systemic lupus erythematosus: a case report.

We report the case of a 61-year-old female who suffered from systemic lupus erythematosus (SLE) and died of a ruptured abdominal aortic aneurysm (AA). She was diagnosed to have SLE at 39 years of age, and was administrated steroids and prostaglandin E(2). From 52 years of age, AA, peripheral arterial occlusion, and multiple organ infarctions appeared repeatedly. At 59 years of age, she was found to be affected by antiphospholipid antibody syndrome (APS). In the following year, expansion of an abdominal AA was identified, but she was given only conservative treatment. In the next year, sudden epigastralgia and dyspnea occurred, and she died. An autopsy revealed multiple AAs up to 11 cm in diameter, one of which showed ruptures, forming a retroperitoneal hematoma. Marked atherosclerosis of the aorta was noted, and she also had aortic dissection accompanied by cystic medial necrosis (CMN). An old myocardial infarction and brain infarction were also confirmed. Although SLE with APS is common, a complication of the disease by CMN, multiple AAs, or ruptured AA has been described in several cases to date. Regarding the etiology of this complicated presentation, we presume synergistic involvement of various factors, such as atherosclerosis and CMN associated with SLE, thrombosis due to APS, and prolonged steroid therapy.

Vesicoenteric Fistula Arising from an Adenocarcinoma of Ectopic Pancreatic Tissue in a Meckel Diverticulum.

We report a case of a vesicoenteric fistula arising from an adenocarcinoma of ectopic pancreatic tissue in a Meckel diverticulum in a 58-year-old man. The patient suffered from refractory micturition pain and increased urinary frequency. Computerized tomography with a contrast agent showed a ring-shaped enhanced mass near the dome of the urinary bladder. Magnetic resonance imaging showed a cystic mass close to the urinary bladder with partly irregular wall and fistula formation to the urinary bladder. Surgical findings showed a Meckel diverticulum in the ileum, which formed a fistula with the urinary bladder, and Meckel diverticulectomy and partial cystectomy were performed. Histological findings revealed a vesicoenteric fistula arising from a papillary adenocarcinoma of ectopic pancreatic tissue in a Meckel diverticulum. The patient has survived without recurrence for more than 4 years since surgery.

Altered expression of cytokeratin 7 and CD117 in transitional mucosa adjacent to human colorectal cancer.

The multi-step progression of colorectal cancer through precancerous lesions (adenoma and dysplasia) is associated with cumulative molecular alterations, a number of which have also been demonstrated to be present in morphologically normal transitional mucosa adjacent to colorectal cancer. The cytoskeletal protein cytokeratin 7 (CK7) and the receptor tyrosine kinase, KIT proto-oncogene receptor tyrosine kinase (CD117), encoded by the proto-oncogene c-Kit, are lacking in normal colorectal crypt epithelium and are aberrantly expressed in a subset of colorectal cancer. The aim of the present study was to evaluate the expression of CK7 and CD117 in morphologically normal transitional mucosa adjacent to colorectal cancer. Immunohistochemical staining for CK7 and CD117 was performed in the mucosa adjacent to five groups of surgically resected colorectal tumors [low-grade adenoma, high-grade adenoma, mucosal adenocarcinoma, small-sized invasive adenocarcinoma (≤2 cm) and large-sized invasive adenocarcinoma (>2 cm)]. CK7 was expressed in the mucosa adjacent to a subset of colorectal tumors, and the positivity ratio increased according to tumor grade from low-grade adenoma up to small-sized invasive adenocarcinoma (61.2%). However, the positivity ratio of CK7 in the mucosa adjacent to the large-sized invasive adenocarcinoma (25.0%) was significantly lower compared with that of the next lower grade. CD117 was also expressed in the mucosa adjacent to a subset of colorectal tumors. In contrast to CK7, the positivity ratio of CD117 increased according to tumor grade from low-grade adenoma all the way through to the large-sized invasive adenocarcinoma (45.0%). Based on these results, the mechanism of CK7 and CD117 expression in the transitional mucosa adjacent to colorectal cancer may be different, and analysis of their individual expression may provide novel insights into the development and progression of colorectal cancer.

Solitary Pulmonary Capillary Hemangioma of Adult Cases: Clinicopathologic Characteristics as an Unrecognized Entity.

Solitary pulmonary capillary hemangioma (SPCH) is a rare disease, first described about autopsy cases in 2000 and about surgically resected cases in 2006. To date, only 9 surgically resected cases have been published in English. Here, we report 7 original cases with surgery (median age, 54 y; 4 females, 2 never-smokers). All patients were asymptomatic, and all nodules were detected by computed tomography (CT). The median (range) size of nodule was 11 (8 to 16) mm. Six of 7 cases showed the part-solid nodule appearance and 1 showed pure ground-glass nodule appearance in CT findings. The growth speed was very slow. No abnormal uptake of fluorine-18 fluorodeoxyglucose was observed in systemic positron-emission CT in all 3 cases we examined. No patients died from SPCH. Histologically, SPCH manifested as a solitary lesion composed of densely proliferating and dilated capillaries without cytologic atypia within the alveolar septa. In addition, capillaries of SPCH spread into the vascular lumen and involved the walls of bronchioles with protrusion into the lumen. Immunohistochemically, capillaries of SPCH uniformly expressed endothelial markers, such as CD31, CD34, and Factor VIII; and α-smooth muscle actin positive cells were also observed. To be accurately diagnosed, especially in intraoperative frozen sections, SPCH should be conceived as an entity that presents as a solitary nodule in CT. We propose that SPCH is an unrecognized benign capillary proliferative disease.

Inflammatory cells in the formation of tumor-related sarcoid reactions.

Tumor-related sarcoid reactions were analyzed in 14 lymph nodes in comparison with sarcoidosis using immunohistochemical markers to lymphocytes (CD3, CD4, CD8, and CD20), myeloid-related protein (MRP) 8 and MRP14 (S100A8 and S100A9), angiotensin I-converting enzyme (CD143), and mature or immature dendritic cells (S100, HLA-DR, fascin, CD83, and CD1a). We found that solitary epithelioid cell granuloma (ECG) first occur between lymph sinus and T-zone and that multiple ECGs mainly occur within T-zone, whereas confluent types often occupy the whole lymph node except some residual lymphoid follicles. This pattern suggests a continuous spread and growth of ECGs in sarcoid reactions along T-zone, where antigen presentation mainly takes place. Irrespective of granuloma type, a constant invasion of freshly recruited MRP8 + and MRP14 + macrophages was observed. Similar to sarcoidosis, angiotensin I-converting enzyme expression was a constant finding in epithelioid and giant cells, suggesting a common inflammatory pathway. An increasing ratio of CD4 + to CD8 + T lymphocytes (r = 0.789, P = .001) and a decreasing number of S100 + and CD83 + dendritic cells (r = 0.787, P = .001) within ECGs correlated with granuloma growth, whereas CD1a + immature dendritic cells were never observed inside ECGs. Our findings show that sarcoid reactions represent a T-cell-mediated immune response, leading to histological appearance and cell distribution similar to sarcoidosis and other granulomatous conditions, but the mechanism is different from dendritic cell-based tumor vaccination. Furthermore, mature dendritic cells occur inside ECGs especially of early sarcoid reactions but may not be required for the enlargement and further maintenance of ECGs, in contrast to CD4 + lymphocytes.

Cavernous Pancreatic Ductal Ectasia with Smooth Muscle Proliferation Causing Recurrent Acute Pancreatitis.

Pancreatic cystic lesions have various etiologies,including pseudocyst (inflammatory cyst), retentioncyst, congenital cyst, and neoplastic cyst (1).Recently, we experienced a case with a uniquepancreatic cyst-like lesion causing recurrent acutepancreatitis. This patient had multiple cystic dilatations of branch pancreatic ducts surrounded by proliferationof smooth muscle tissue, with neither neoplastic nor inflammatory changes. To our knowledge, there are no previous reports of such a case.

Serum level and immunohistochemical expression of vascular endothelial growth factor for the prediction of postoperative recurrence in renal cell carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis. One of the functions of VEGF is to regulate neovascularization in clear cell renal cell carcinoma (CCRCC). The objective of our study was to examine whether before nephrectomy serum levels of VEGF or expression of VEGF using immunohistochemistry (IHC) could predict postoperative recurrence in nonmetastatic CCRCC. RESULTS: Twelve patients (14.5%) had recurrence during a mean follow-up of 52.6 ± 31.2 months. The serum VEGF level was significantly higher in patients with recurrence than in those without recurrence (P = 0.038). High serum VEGF levels were above 416 pg/mL; this value was chosen based on a receiver operating characteristic analysis. The recurrence-free survival rate in patients with a high serum VEGF level was significantly lower than in those with a low serum VEGF level (P = 0.003). In total, tumors from 26 patients (31.3%) showed overexpression of VEGF using IHC. The recurrence-free survival rate in the IHC-positive group was significantly lower than that in the IHC-negative group (P = 0.044). Multivariate analysis indicated that preoperative serum VEGF levels (P = 0.013) and female gender (P = 0.004) were independent predictors of postoperative recurrence in nonmetastatic CCRCC. CONCLUSIONS: Preoperative serum VEGF levels is a useful predictor compared with IHC analysis of VEGF of postoperative recurrence in nonmetastatic CCRCC.

AP-VAS 2012 case report: a case of systemic MPO-ANCA-associated vasculitis that demonstrated brain infarction and immunohistochemically MPO-positive capillaries.

We present a case of an aged male with myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis with onset of brain infarction that demonstrated immunohistochemically MPO-positive capillaries at autopsy. The patient initially presented with gait difficulty and right-sided weakness. Since an imaging study revealed brain infarction, he was admitted to our hospital and medicated by antiplatelet agents. Continuous fever and elevated serum C-reactive protein (CRP), hematuria of glomerular origin, renal dysfunction, and high serum titer of MPO-ANCA were detected. Systemic toxicoderma appeared, and skin biopsy revealed small-vessel vasculitis; thus, he was diagnosed with MPO-ANCA-associated vasculitis. Steroid therapy (methylprednisolone 30 mg/day) was started, and general status improved. However, he died of shock 6 days after the start of the therapy. Autopsy revealed massive retroperitoneal hemorrhage with necrotizing small-vessel vasculitis in systemic organs including retroperitoneum, skin, brain, testes, and kidneys. Immunohistochemically, infiltration of MPO-positive white blood cells into the capillaries was occasionally observed, along with the features of MPO-positive capillaries. Cerebrovascular involvement of MPO-ANCA-associated vasculitis is rare compared with renal and pulmonary manifestations, having been reported to occur in up to 4 % of patients. Furthermore, as we have recently reported, MPO-immunopositive capillaries may appear only during the hyperacute stage of the disease. Therefore, the present case represents the unique combination of these two rare manifestations.