Both serum and tissue Galectin-1 levels are associated with adverse clinical features in neuroblastoma.

BACKGROUND: Neuroblastoma is one of the most common pediatric solid tumors. Although the 5-year overall survival rate has increased over the past few decades, high-risk patients still have a poor prognosis due to a lack of biomonitoring therapy. This study was performed to investigate the role of Galectin-1 in neuroblastoma biomonitoring therapy. PROCEDURE: A tissue microarray containing 37 neuroblastoma tissue samples was used to evaluate the correlation between Galectin-1 expression and clinical features. Blood samples were examined to better understand whether serum Galectin-1 (sGalectin-1) could be used for biomonitoring therapy. Kaplan-Meier analysis and ROC analysis was conducted to distinguish the outcome associated with high or low expression of Galectin-1 in patients with neuroblastoma. RESULTS: Increased Galectin-1 expression was found in neuroblastoma and it was further demonstrated that elevated tissue Galectin-1 expression was related to INSS stage, histology, bone marrow metastasis, and poor survival. sGalectin-1 levels were higher in newly diagnosed patients with neuroblastoma than healthy subjects. Patients with elevated sGalectin-1 through treatment cycles correlated with the poor chemo-responses and tended to have worse outcomes, such as metastasis or stable tumor size, whereas gradually decreasing sGalectin-1 levels correlated with no observed progression in clinical symptoms. CONCLUSIONS: Tissue and serum Galectin-1 levels were associated with adverse clinical features in patients with neuroblastoma, and sGalectin-1 could be a potential biomarker for monitoring therapy.

GIST Manifesting as a Retroperitoneal Tumor: Clinicopathologic Immunohistochemical, and Molecular Genetic Study of 112 Cases.

Most gastrointestinal stromal tumors (GISTs) occur in the tubular gastrointestinal (GI) tract, but some present apparently outside the GI tract. In this study, we analyzed 112 GISTs located in the retroperitoneum. These tumors occurred in 55 women and 57 men with a median age of 65 years (range: 21 to 89 y). On the basis of clinically or histologically detected connections to GI tract, 15 tumors were considered likely of gastric, 9 duodenal, and 13 of small intestinal origin. The remaining cases were categorized by location as peripancreatic (n=25), pelvic (n=11), mesenteric (n=4), and of unspecified/miscellaneous sites (n=35). The tumors varied in size 3 to 35 cm (median, 15 cm) and by mitotic rate per 5 mm, 0 to >100 (median, 10). Histologically the tumors apparently arising outside the GI tract had features of intestinal (n=41) and gastric GISTs (n=25); 9 cases had indeterminate histology. The histologic variants included spindled, epithelioid, vacuolated, nested, and myxoid potentially simulating other tumors such as liposarcoma and solitary fibrous tumor. Most GISTs were KIT-positive (106/112 cases), and the remaining 6 tumors were DOG1/Ano1-positive. Five cases showed focal nuclear positivity for MDM2. KIT mutations were detected in 42/59 cases, and PDGFRA mutations in 4/16 KIT wild-type and 3/5 of the KIT-negative tumors analyzed. One pelvic retroperitoneal GIST was succinate dehydrogenase deficient. All 79 patients were dead at last follow-up with a median survival of 14 months, with few survivals >5 years. Only operable versus inoperable tumor was a statistically favorable factor in univariate analysis (P<0.01). In multivariate analysis, mitotic rate >50/5 mm was significant for a shorter survival (hazard ratio, 5.25; 95% confidence interval, 1.65-16.8; P<0.01). Histologic and clinicopathologic similarity of extragastrointestinal retroperitoneal GISTs with GISTs of GI tract suggests their GI tract origin. Potentially overlapping features between GIST and other retroperitoneal tumors necessitate use of multiple diagnostic markers and molecular genetic studies.

A subset of fat-predominant angiomyolipomas label for MDM2: a potential diagnostic pitfall.

Angiomyolipomas (AMLs) are typically benign mesenchymal tumors with variable histologic composition. Fat-predominant AMLs can mimic well-differentiated liposarcomas (WDLSs) both radiographically and histologically because of the abundance of fat with admixed atypical cells resembling lipoblasts. However, the treatment and prognosis of AMLs and WDLSs are vastly different. Immunohistochemistry for murine double minute 2 (MDM2) has been used to support a diagnosis of WDLS; however, MDM2 labeling has not been specifically evaluated in fat-predominant AMLs. Here, we evaluated MDM2 immunohistochemistry in 36 AMLs (including 14 conventional AMLs, 13 fat-predominant AMLs, 6 fat-rich AMLs, 3 epithelioid AMLs) and 10 WDLSs. In addition, we labeled cases for HMB45, calponin, or actin, which are immunostains traditionally used to label AML. We performed fluorescence in situ hybridization (FISH) for MDM2 amplification on selected cases. By immunohistochemistry, 14% (5/36) of AMLs were MDM2+, including 23% (3/13) of fat-predominant AMLs. All MDM2+ AMLs evaluated by FISH (n=4) were negative for MDM2 amplification. By immunohistochemistry, 90% of WDLSs were MDM2+, and both MDM2+ WDLSs evaluated by FISH (n=2) were MDM2 amplified. All 36 AMLs labeled with HMB45 and calponin or actin. No WDLS labeled with HMB45; however, 80% of WDLSs labeled with calponin or actin. Although uncommon, MDM2 labeling is seen in a subset of fat-predominant AMLs and is a potential diagnostic pitfall in the evaluation of fatty tumors of the retroperitoneum. HMB45 is more sensitive and specific for AML than calponin or actin, and an immunopanel containing both HMB45 and MDM2 may be warranted to distinguish between fat-predominant AML and WDLS in histologically ambiguous cases.

Giant intra-abdominal mature cystic teratoma (dermoid cyst) in an adult man, with male genitourinary tissue including prostatic and penile elements.

We describe a case of a giant intra-abdominal mature cystic teratoma in a 36-year-old man, which comprised typical features of differentiated teratoma/dermoid cyst but which contained a macroscopic rudimentary penis, with vasoformative erectile tissue-like structures consistent with corpora cavernosa, as well as scrotal-type skin and prostatic tissue. The genitourinary structures were well formed both grossly and microscopically and sharply demarcated from the rest of the neoplasm, which comprised typical differentiated teratoma, without any other macroscopic foci of organoid differentiation or of other histologic differentiation. The plasticity of the cells of differentiated teratoma, which enables it to undergo multidirectional differentiation, is well recognized, but the factors determining this distinct path of differentiation remain to be established.

ZBTB16: a novel sensitive and specific biomarker for yolk sac tumor.

Although the function of zinc finger and BTB domain containing 16 (ZBTB16) in spermatogenesis is well documented, expression of ZBTB16 in germ cell tumors has not yet been studied. The aim of this study was to investigate the immunohistochemical expression and diagnostic utility of ZBTB16 in germ cell tumors. A total of 67 adult germ cell tumors were studied (62 testicular germ cell tumors, 2 ovarian yolk sac tumors, 1 mediastinal yolk sac tumor, and 2 retroperitoneal metastatic yolk sac tumors). The 62 testicular primary germ cell tumors are as follows: 34 pure germ cell tumors (20 seminomas, 8 embryonal carcinomas, 2 teratomas, 1 choriocarcinoma, 1 carcinoid, and 2 spermatocytic tumors) and 28 mixed germ cell tumors (composed of 13 embryonal carcinomas, 15 yolk sac tumors, 15 teratomas, 7 seminomas, and 3 choriocarcinomas in various combinations). Thirty-five cases contained germ cell neoplasia in situ. Yolk sac tumor was consistently reactive for ZBTB16. Among the 15 testicular yolk sac tumors in mixed germ cell tumors, all displayed moderate to diffuse ZBTB16 staining. ZBTB16 reactivity was present regardless of the histologic patterns of yolk sac tumor and ZBTB16 was able to pick up small foci of yolk sac tumor intermixed/embedded in other germ cell tumor subtype elements. Diffuse ZBTB16 immunoreactivity was also observed in 2/2 metastatic yolk sac tumors, 1/1 mediastinal yolk sac tumor, 2/2 ovarian yolk sac tumors, 2/2 spermatocytic tumors, 1/1 carcinoid, and the spermatogonial cells. All the other non-yolk sac germ cell tumors were nonreactive, including seminoma (n=27), embryonal carcinoma (n=21), teratoma (n=17), choriocarcinoma (n=4), and germ cell neoplasia in situ (n=35). The sensitivity and specificity of ZBTB16 in detecting yolk sac tumor among the germ cell tumors was 100% (20/20) and 96% (66/69), respectively. In conclusion, ZBTB16 is a highly sensitive and specific marker for yolk sac tumor.

[An Abnormal Alpha-Fetoprotein Fractionation Provides Additional Information: A Case of Retroperitoneal Germ Cell Tumor Accompanied by Liver Cirrhosis Type C].

Most of germ cell tumor is gonadal origin. However 5% of malignant germ cell tumors appear in extragonadal organs. Because extragonadal germ cell tumors (EGGCTs) are found anywhere on the midline such as pineal gland, mediastinum and retroperitoneum, the origin of this type of tumor is controversial. EGGCTs are often seen between childhood and young adult; an elderly patient with EGGCT is rarely met. Here we report a case that an abnormal alpha-fetoprotein (AFP) fractionation pattern was helpful for diagnosis of retroperitoneal germ cell tumor. A presenile man with hepatic cirrhosis caused by chronic hepatitis C showed an intraperitoneal tumor-like mass on computed tomography and thus hepatocellular carcinoma was suspected. A serological test re- vealed elevated total AFP level and AFP-L3%. The latter is the proportion of fucosylated AFP on the lectin-affinity based fractionation. Noticeably the fractionation pattern of AFP of this patient was abnormal, sug- gesting a diversity of lectin-affinity of AFP in germ cell tumors. This patient also showed an atypical in- crease in beta human chorionic gonadotropin (8hCG). We suggest the measurement of 6hCG for early differ- ential diagnosis of retroperitoneal germ cell tumor and hepatocellular carcinoma when an abnormal AFP frac- tionation pattern was detected in a patient with suspected hepatocellular carcinoma. [Short Communication].

SUCCESSFUL TREATMENT OF PULMONARY AND LYMPHATIC MANIFESTATIONS OF LYMPHANGIOLEIOMYOMATOSIS WITH SIROLIMUS.

Lymphangioleiomyomatosis (LAM) is a rare, progressive, diffuse cystic lung disease predominantly affecting women of child bearing age. Recently treatment with sirolimus was shown to stabilize lung function decline and improve quality of life in patients with LAM. We treated three premenopausal women suffering from LAM manifesting as diffuse cystic lung disease, chylous effusions, and lymphangioleioyomas with sirolimus (1-3 mg a day; sirolimus trough levels 2.9-8.5 ng/ml). All three patients had a remarkable response to sirolimus, with resolution of effusions, improvement in lung function and shrinking of abdominal lymphangioleiomyomas. Our case series further complements the literature in that sirolimus is a safe and effective treatment for LAM and its lymphatic manifestations.

Müllerianosis with Intestinal Metaplasia: A Case Report.

Müllerianosis or Müllerian choristomas are developmental alterations that consist of an organoid structure with normal Müllerian tissue. We present a 62-year-old patient diagnosed on ultrasound scanning and on CT scan of bilateral ovarian cysts. During surgery, a left ovarian cyst and retroperitoneal tumor (adhered to sigmoid serous surface) were found. On histological examination, the tumor corresponded with a Müllerian choristoma showing endometrial, endosalpingeal and endocervical epithelium, with foci of intestinal metaplasia, a phenomenon not described in the literature.

Extragonadal malignant germ cell tumors: a clinicopathological and immunohistochemical analysis of 48 cases at a single Chinese institution.

Primary extragonadal malignant germ cell tumors (EMGCTs) are rare and characterized by the location in the midline of the body, including mediastinum, CNS, retroperitoneum and coccyx. EMGCTs present with different clinical and biologic characteristics in different tumor locations. Accurately diagnosing MEGCTs would be very difficult by performing on HE staining alone, and requires immunohistochemical verification. This study was to investigate the biological feature of EMGCTs and diagnostic value of immunohistochemical markers OCT3/4, CD117, PLAP, AFP, ß-HCG and CD30 in EMGCTs. A retrospective study was performed on 48 patients with EMGCTs. EMGCTs were found to occur predominantly in males, especially for mediastinal MGCTs. The tumor locations included mediastinum, CNS and retroperitoneum. The mediastinum and CNS were the most common sites of EMGCTs. Seminoma/germinomas (64.6%) was the most common histological subtypes of EMGCTs. Chest pain, dyspnea, cough and fever were the most common clinical presentations in mediastinal MGCTs. Headache, visual disturbances, endocrine abnormalities, and signs of increased intracranial pressure were common clinical symptoms in CNS MGCTs. Abdominal mass with or without pain, backache and weight loss were common clinical presentations in retroperitoneal MGCTs. PLAP, CD117 and OCT3/4 were highly expressed in seminomas/gernimomas. CD30, EMA and CK AE1/3 staining were positive in embryonal carcinoma. AFP and ß-HCG positive staining are characteristic in yolk sac tumors and choriocarcinoma, respectively. Patients with seminomas/germinomas had a better prognosis than those with NS/G-GCTs. Our finding suggests that the accurate diagnosis of EMGCTs is critical not only for predicting the tumor progression but also for patient management. Immunohistochemical markers have become an important tool in the diagnosis and differential diagnosis of EMGCTs.

Refractory diarrhea: A paraneoplastic syndrome of neuroblastoma.

Neuroblastoma (NB) is the most common extracranial solid tumor in children. Diarrheal NB is quite rare and is not easy to diagnose in the early stage. Six cases of diarrheal NB in our hospital treated from 1996 to 2006 were retrospectively analyzed, including characteristics such as electrolyte imbalance, pathologic features, vasoactive intestinal peptide (VIP) immunohistochemical staining results, treatment, and prognosis. All patients were boys with 3-8 loose or watery stools each day and routine fecal tests were normal. Abdominal tumors were identified by B-ultrasound. Drugs were ineffective. Three patients underwent surgery, and the remaining three patients received surgery and chemotherapy. Diarrhea stopped after treatment in five patients. Two patients died due to intractable hypokalemia. The tumor was located in the adrenal gland in four patients, in the upper retroperitoneum in one patient, and in the presacral area in one patient. Pathologic findings were NB and ganglioneuroblastoma. Five patients were at clinical stage I-II, and one was at stage III. Four patients survived (followed-up for 6 mo to 4 years). Immunohistochemical staining for VIP was positive. Refractory diarrhea is a paraneoplastic syndrome of NB and is rare. Patients aged 1-3 years who present with chronic intractable diarrhea should be followed closely. Intractable diarrhea, hypokalemia, and dysplasia are the initial clinical manifestations. Increased VIP is characteristic of this disease. Potassium supplementation plays a vital role in the treatment procedure, especially preoperatively. The prognosis of diarrheal NB is good following appropriate treatment.

Primary retroperitoneal mucinous cystadenoma: A case report.

Primary retroperitoneal mucinous cystic tumors are extremely rare. These tumors can be classified as a primary retroperitoneal mucinous cystadenoma with or without borderline malignancy or primary retroperitoneal mucinous cystadenocarcinoma. The most common of these is primary retroperitoneal mucinous cystadenoma, which almost always occurs in female patients; only ten cases have been reported in males. The most common clinical findings for this tumor type include nonspecific abdominal pain and a palpable abdominal mass. A definitive diagnosis is usually obtained from histopathology after surgical excision. Here, we report the case of a 60-year-old female patient who complained of abdominal pain that had been present for 3 mo and presented with a palpable abdominal mass. Multidetector computed tomography scanning revealed a large, unilocular cystic mass in the left retroperitoneal space. Surgical intervention was performed and the tumor was completely removed. Histopathologic examination confirmed that the tumor was a primary retroperitoneal mucinous cystadenoma. Two years after surgery, the patient remains disease free.

Laparoscope resection of retroperitoneal ectopic insulinoma: a rare case.

Ectopic insulinoma is a very rare and dormant tumor. Here we report the case of a 79-year-old female who presented with repeated episodes of hypoglycemia and was diagnosed with insulinoma based on laboratory and imaging examinations. Computed tomography and positron emission tomography revealed a tumor in the retroperitoneum under and left of the hepatoduodenal ligament, which was resected successfully using a laparoscopic approach. Pathologic results revealed an ectopic insulinoma, which was confirmed immunohistochemically. Ectopic insulinomas are accompanied by hypoglycemia that can be misdiagnosed as drug- or disease-induced. These tumors are difficult to diagnose and locate, particularly in atypical cases or for very small tumors. Synthetic or targeted examinations, including low blood glucose, elevated insulin, proinsulin, and C-peptide levels, 48-h fasting tests, and relevant imaging methods should be considered for suspected cases of insulinoma. Surgery is the treatment of choice for patients with insulinoma, and laparoscopic resection is a feasible and effective method for select ectopic insulinoma cases.

Myogenic differentiation and histologic grading are major prognostic determinants in retroperitoneal liposarcoma.

The aim of the present work was to improve the understanding of the impact of malignancy grade and myogenic/rhabdomyoblastic differentiation on the natural course of retroperitoneal liposarcoma. All consecutive patients affected by primary well-differentiated (WD)/dedifferentiated (DD) retroperitoneal liposarcoma, surgically treated at our institution between January 2002 and December 2011, were retrospectively evaluated. Tumors were stained for mdm2 and 5 myogenic markers (smooth muscle actin-α, h-caldesmon, calponin, desmin, myogenin). The French National Federation of the Centers for the Fight Against Cancer (FNCLCC) grading system was applied. Overall survival, crude cumulative incidence of local recurrence, and distant metastases were calculated. Multivariable analyses were carried out. A total of 144 patients were identified. Median follow-up was 68 months (interquartile range: 46 to 104 mo). Fifty-two patients were affected by WD/G1 and 92 by DD liposarcoma. Among the latter, 60 were grade G2 and 32 G3. Myogenic differentiation was present in 54 cases (8/52 WD/G1, 27/60 DD/G2, 18/32 DD/G3). Seven cases had a rhabdomyoblastic DD component (1/60 DD/G2 and 6/32 DD/G3). Five-year overall survival rates were 93%, 57%, and 21% for WD/G1 liposarcoma, G2 DD, and G3 DD liposarcoma, respectively, and 75%, 42%, and 29% for liposarcoma without myogenic differentiation, with myogenic differentiation, with rhabdomyoblastic differentiation, respectively (P<0.001). Of note, 5/6 patients affected by G3 DD liposarcoma with a rhabdomyoblastic component died within 8 months. FNCLCC grade and myogenic differentiation significantly predicted the outcome of retroperitoneal liposarcoma. These should be factored into treatment decision-making and possibly used to stratify patients in clinical trials.

[Dedifferentiated Liposarcoma with Peculiar Meningothelial-Like Whorling and Metaplastic Bone Formation, Case Report]. / Meningotelyal Benzeri Girdapsi Yapilar ve Metaplastik Kemik Yapimi ile Karakterli Dediferansiye Liposarkom Olgusu.

Dedifferentiated liposarcoma represents a both morphologically and biologically fascinating lesion in which transition from low-grade to high-grade nonlipogenic morphology within a well-differentiated liposarcoma is observed. A peculiar form of dedifferentiated liposarcoma characterized by a nonlipogenic component with a meningothelial- like whorling pattern of growth and metaplastic bone formation has been described. A 59-year-old man presented with a pelvic retroperitoneal mass measuring 13x10x8 cm. Histopathologically the mass consisted almost entirely of a dedifferentiated nonlipogenic component with meningothelial-like whorling pattern, metaplastic cartilage and bone. Dedifferentiated liposarcoma with meningothelial- like whorling pattern has rarely been encountered. Here, we report this case because of the problems in differential diagnosis especially for cases that have an extensive dedifferentiated component and the uncertainty of the biological behavior of these tumors.

CREPT expression correlates with poor prognosis in patients with retroperitoneal leiomyosarcoma.

Retroperitoneal leiomyosarcomas (LMSs) are rare gynecological malignancies that display poor prognosis and high mortality. Cell cycle-related and expression-elevated protein in tumor (CREPT) is an oncogene that is involved in the regulation of many cell cycle-related proteins. However, its distribution and clinical significance in retroperitoneal LMS remains poorly understood. This study assessed the histological classifications of postoperative tumor samples from 71 cases of retroperitoneal LMS that were collected at The General Hospital of the People's Liberation Army from January 1998 to December 2012. We found that more than half of the patients displayed positive expressions of CREPT, Ki-67 and PCNA via immunohistochemical analysis. The expression of CREPT correlated with histological grade (P = 0.044), and the PCNA expression level correlated with the differentiation of tumor cells and histological grade (P < 0.001 and P = 0.009, respectively). Multivariate analysis showed that survival was associated with histological grade and the expression level of CREPT (P = 0.011 and P = 0.012, respectively). Kaplan-Meier analysis showed that the patients lacking CREPT expression exhibited significantly longer overall postoperative survival (median, 60.0 months) than the patients displaying CREPT expression (median, 33.0 months), and CREPT expression correlated with distant recurrence within 5 years after surgery (P = 0.004). Western blot analyses showed that CREPT was more strongly expressed in the retroperitoneal LMS tumor tissue than in paired control tissue. Based on the above data, we concluded that CREPT displays unique immunostaining for retroperitoneal LMS tissue and can be used to supplement other currently available retroperitoneal LMS markers.

Recurrence of retroperitoneal Merkel cell carcinoma. A case report.

BACKGROUND: Merkel cell carcinoma (MCC) is a neuroendocrine malignant neoplasm that usually has its primary location on the skin. It often metastasizes to lymph nodes, liver, lungs, bones and brain. Actually there have been few cases of MCC of the retroperitoneal region without a primary skin lesion. CASE PRESENTATION: Our case is a male of 55 year old who initially underwent a partial resection (R1) of a bulky pelvic mass; the histopathological analysis and the immunoistochemistry showed the presence of neuroendocrine Merkel cells. The patient underwent 6 cycles of postoperative chemotherapy (carbon platinum and etoposide) and adjuvant radiotherapy. Afterwards the patient underwent surgery again with the complete resection of the tumour. DISCUSSION: The histopatological and immunoistochemistry analysis of the first and the second surgical samples confirmed the diagnosis of a retroperitoneal high-grade neuroendocrine carcinoma with a high mitosis index. The immunoistochemistry profile showed neoplastic cell with: CD 20+, synaptophysin +, TTF-1-, neurofilaments +, CK 7-, chromogranin, Ki67 90%. In the patient's medical history no skin localizations were mentioned. CONCLUSION: The hypothesis of a MCC with a primary retroperitoneal localization has been strength by the histopathological and immunoistochemistry analysis of two intra-operative samples from two different surgical procedure and from the absence of either a primary skin location or of secondary recurrences. Is therefore reinforced the theory that from a cell into a retroperitoneal lymph node can arise a retroperitoneal mass originating a Merkel cell tumour.