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Objective@#To investigate the difference between routine hematoxylin-eosin (HE) staining and immunohistochemistry in diagnosing metastatic melanoma in sentinel lymph node (SLN) metastases, and to evaluate the association of SLN tumor burden with the status of non-sentinel lymph nodes (NSLN).@*Methods@#126 melanoma patients were treated with SLN biopsy and further examined with immunohistochemistry at Fudan University Shanghai Cancer Center between 2010 and 2016, and the status of SLN was respectively estimated by HE stain and immunohistochemistry (S-100 protein, HMB45, Melan A and SOX10). In 39 patients who were treated with complete lymph node dissection, characteristics of SLN tumor burden (maximum diameter of the tumor deposit, tumor penetrative depth and the microanatomic location of the metastasis) and the associations of SLN tumor burden with the involvement of NSLN were all evaluated.@*Results@#Of the total 126 cases, 33 (26.2%) were positive by HE staining and 49 (38.3%) were positive by immunohistochemistry. S-100 protein was positive in 48 out of 49 cases (98.0%). HMB45 was positive in 46 out of 49 cases (93.9%). Melan A was positive in 47 out of 49 cases (96.0%). SOX10 was positive in 8 out of 8 cases. The outcome indicated that the application of immunohistochemistry identified positive SLN missed by HE stain in about 12.1% of cases. Of the 39 patients who were treated with complete lymph node dissection, six showed metastases in NSLN. The frequency of metastases in NSLN was 15.4% (6/39) when SLN was positive. Additionally, the frequency of metastases in NSLN in cases with SLN metastatic deposits ≤2 mm was significantly lower than that in cases with SLN metastatic deposits >2 mm; eight cases with SLN metastatic deposits <0.2 mm had no additional positive NSLN.@*Conclusions@#The findings suggest that immunohistochemistry could effectively improve the detection of positive SLN in melanoma. Cases with SLN metastatic deposits ≤2 mm are less likely to have further metastases in NSLN. There is a need for prospective large-population based studies to identify a subgroup of SLN positive patients who can safely be spared complete lymph node dissection.
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Objective@#To study the clinicopathologic features, differential diagnosis and prognosis of lentigo maligna (LM) and lentigo maligna melanoma (LMM).@*Methods@#Histopathologic evaluation and immunohistochemical study by HRP multimer method were carried out in 24 cases of LM and LMM from 2012 to 2017 at Fudan University Shanghai Cancer Center. The clinical information and follow-up data were analyzed.@*Results@#Of total 24 cases, there were 7 cases of LM and 17 cases of LMM; 10 males and 14 females. The age of patients ranged from 32 to 88 years (mean 67 years). The male-to-female ratio was 1.0∶1.4. Tumors were all located on head and face. Clinically, all patients presented with mottled light brown or sepia macule located on head and face for a long time, and some of them followed by nodules or ulceration within the lesion. The diameter of lesions ranged from 0.5 to 3.0 cm. Microscopically, LM and in-situ component of LMM were all characterized by a predominantly junctional proliferation of atypical melanocytes with marked pleomorphism, frequently extending down the walls of hair follicles and sweat ducts. Multinucleate cells were frequently present. The invasive components of LMM mainly consisted of atypical melanocytic spindle cells (13 cases, 76.5%), and the mean Breslow thickness was 1.2 mm (0.1-2.7 mm). The lesions of LM/LMM were generally associated with severe actinic damage, scattered infiltration of lymphocytes and melanophages. Statistically, the number of cases whose diameter of lesion ≥0.6 cm, mitotic rates ≥4/mm2 and nests of melanocytes within epidermis in group of LMM were significantly more than those in group of LM. Immunohistochemically, atypical melanocytes in LM and LMM were generally positive for S-100, HMB45, PNL2, Melan A and SOX-10. Follow-up was available in all cases, ranging from 1 to 64 months. Only one out of 23 patients with wide surgical excision had local recurrence, and the remaining 22 patients were all alive with no evidence of disease. One LM patient who was merely treated with biopsy was alive with disease progression after 20 months follow-up.@*Conclusions@#LM/LMM is a special subtype of melanoma predominantly located on the sun-exposed skin of elderly people. Recognition of its specific histologic features can help distinguish with sun-damaged diseases and other subtypes of melanoma. The prognosis of LM/LMM patients treated with surgical excision is considered relatively favorable. However, long term follow-up should be recommended in patients with LM/LMM because of high recurrence rates indicated by previous studies.
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Objective@#To describe the clinicopathologic features, diagnosis and differential diagnosis of ovarian carcinoid tumors.@*Methods@#A retrospective chart review was performed of all patients diagnosed with primary ovarian carcinoid tumors at Fudan University Shanghai Cancer Centre from 2007 to 2017.@*Results@#The histologic analysis of these carcinoid tumors revealed 3 were insular, 1 was trabecular, 1 was mucinous, and 10 were strumal. Histologic features of insular and trabecular carcinoid were similar to other parts of the neuroendocrine tumor. Strumal carcinoid was composed of thyroid tissue intimately admixed with carcinoid tumor, showing trabecular pattern. Mucinous carcinoid was resembles Krukenberg tumor. Most ovarian carcinoid tomours were diffusely positive with at least one neuroendocrine marker, especially synaptophysin (14/14) and CD56(9/10). The median follow-up time was 53 months, 1 patient with squamous-cell carcinoma of cervixrecur rence in vaginal after 37 months, and only 1 patient died of disease. The remaining patients were disease-free survival.@*Conclusions@#Primary carcinoid of the ovary is a very rare low grade malignant monodermal teratomas and somatic-type tumours arising from a dermoid. The diagnosis and differential diagnosis mainly relies on the histopathologic characteristics and the immuno-phenotype. Primary ovarian carcinoid almost always exhibit a benign clinical behavious except mucinous carcinoid.
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Objective To retrospectively investigate the characteristics of background parenchymal enhancement(BPE)in the contralateral breast following neoadjuvant chemotherapy(NAC)and whether BPE could help predict tumor response in early stage of advanced breast cancer. Methods Data from 161 patients who were diagnosed with unilateral breast cancer and then underwent NAC before surgery were analyzed retrospectively from August 2014 to December 2016.All the patients underwent both bilateral breast MRI scan with contrast enhancement. Two experienced radiologists independently categorized the patients' levels of BPE into four categories (1=minimal, 2=mild, 3=moderate, 4=marked) at baseline and after the 2nd cycle of NAC. All the patients were divided in to pathologic complete response (pCR) group and non-pCR group according to the histopathologic tumour response.The status of estrogen receptor(ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) were recorded before underwent NAC.The t test and Pearson chi-squared test were used to compare the baseline characteristics of the pCR and Non-pCR groups.The kappa test was used to test the inter-observer agreement.The Wilcoxon test was used to test for changes of BPE categories after NAC.The Mann-Whitney U test was used to test the difference of BPE between pre-and post-menopausal status. Associations were evaluated using Binary logistic regression models. Results Fifty nine patients achieved pCR, and 102 patients had residual disease (non-pCR). Age, tumor size, distribution of size, menopausal status and lymph node showed no significance between pCR and non-pCR groups(all P>0.05),while only ER/PR status and HER2 status had a significant difference (P>0.05 in both). Inter-observer agreement regarding BPE categorization was moderate and substantial before and after NAC(Kappa value 0.644 and 0.708).The level of BPE was higher in premenopausal than post-menopausal women both at baseline and after the 2nd cycle of NAC(P<0.01). Decreased BPE was observed in 106 cases(premenopausal 60 cases and postmenopausal 46 cases),and no change in BPE were observed in 55 cases (premenopausal 27 cases and postmenopausal 28 cases). A significant reduction in BPE was observed after the 2nd NAC cycle in the overall cases, pre-and post-menopausal cases (all P<0.01). Logistic model showed that hormonal receptor (HR) negative and HER-2 receptor at baseline and the change of BPE after NAC were the independent factors for predicting pCR. Conclusions Regardless of the menopausal status, BPE showed a reduction after NAC, and it can serve as an additional imaging biomarker of tumour response at an early stage of NAC.
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Objective@#To evaluate the sensitivity, specificity and clinical value of anti-BRAF V600E antibody (clone VE1) in detection of the BRAF V600E mutant in formalin-fixed and paraffin-embedded (FFPE) melanoma specimens by immunohistochemical (IHC) methods.@*Methods@#A total of 50 melanoma samples collected between 2008 and 2016 from 40 patients were analyzed for BRAF mutation (exon 15) by DNA sequencing using FFPE. These tissues were immunostained with VE1 antibody, and the results were analyzed and compared with those by DNA sequencing.@*Results@#By DNA sequencing, 36 cases showed BRAF mutation while others were BRAF wild type. Among the 36 cases with BRAF mutation, 32 harbored BRAF V600E, two harbored BRAF V600K, one had BRAF K601E and one had BRAF D594N, respectively. IHC staining showed 30 specimens were VE1 positive, while 19 were negative. The determination of IHC result for one case was obscured by heavy pigments. Of the BRAF-mutated specimens, four specimens with BRAF mutation other than V600E were all negative for VE1. The sensitivity and specificity of the VE1 immunostaining was 96.8% and 100.0% respectively.Concordance of BRAF V600E detection between immunostaining and DNA sequencing was 98.0%(48/49).@*Conclusions@#High sensitivity and specificity for VE1 immunostaining in detecting BRAF V600E in melanomas are demonstrated. It is a rapid and cost-effective method for detecting BRAF V600E mutations in melanoma patients. Hence, VE1 immunostaining can be used as an important screening method for BRAF mutation in laboratories.
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Background and purpose: Primary pulmonary myxoid sarcoma (PPMS) is a very rare lung tumor that has recently been shown to harbor EWSR1-CREB1 translocation. This study aimed to investigate the clinicopatho-logical characteristics and differential diagnosis of PPMS. Methods: The clinical and pathological features of 6 cases of PPMS with EWSR1 gene rearrangement were reviewed. Immunohistochemistry and fluorescence in situ hybridization (FISH) study were performed. Results: Six patients were enrolled in this study, including 4 male patients and 2 female patients with an age range of 23 to 64 years (median age, 44 years). All tumors involved pulmonary parenchyma, with a predominant endobronchial component in 1 and adjacent to bronchus in 5 patients. Microscopically, the tumor was lobulated and composed of cords of polygonal, spindle cells within myxoid stroma. Tumors were immunoreactive for only Vimentin and weakly focal for epithelial membrane antigen (EMA). All tumors were shown to harbor EWSR1 gene rearrangement by FISH. Follow-up of all patients showed that 1 patient developed a pleura and bone metastasis but was still alive and 5 were disease-free after 4-29 months. Conclusion: PPMS is an extremely rare sarcoma with low-grade malignant potential. This is characterized by distinct histological features and EWSR1 gene rearrangement. It is important that understanding tumor spectrum and genetic feature can contribute to diagnosis and differential diagnosis of PPMS.
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OBJECTIVE: Distal pancreatectomy with splenectomy may be required for optimal cytoreductive surgery in patients with epithelial ovarian cancer (EOC) metastasized to splenic hilum. This study evaluates the morbidity and treatment outcomes of the uncommon procedure in the management of advanced or recurrent EOC. METHODS: This study recruited 18 patients who underwent distal pancreatectomy with splenectomy during cytoreductive surgery of EOC. Their clinicopathological characteristics and follow-up data were retrospectively analyzed. RESULTS: All tumors were confirmed as high-grade serous carcinomas. The median diameter of metastatic tumors located in splenic hilum was 3.5 cm (range, 1 to 10 cm). Optimal cytoreduction was achieved in all patients. Eight patients (44.4%) suffered from postoperative complications. The morbidity associated with distal pancreatectomy and splenectomy included pancreatic leakage (22.2%), encapsulated effusion in the left upper quadrant (11.1%), intra-abdominal infection (11.1%), pleural effusion with or without pulmonary atelectasis (11.1%), intestinal obstruction (5.6%), pneumonia (5.6%), postoperative hemorrhage (5.6%), and pancreatic pseudocyst (5.6%). There was no perioperative mortality. The majority of complications were treated successfully with conservative management. During the median follow-up duration of 25 months, nine patients experienced recurrence, and three patients died of the disease. The 2-year progression-free survival and overall survival were 40.2% and 84.8%, respectively. CONCLUSION: The inclusion of distal pancreatectomy with splenectomy as part of cytoreduction for the management of ovarian cancer was associated with high morbidity; however, the majority of complications could be managed with conservative therapy.
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Cytoreduction Surgical Procedures , Disease-Free Survival , Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/mortality , Pancreatectomy/adverse effects , Postoperative Complications/epidemiology , Splenectomy/adverse effects , Splenic Neoplasms/pathologyABSTRACT
Objective The aim of this study is to evaluate the safety and efficacy of partial pancreatectomy as part of primary cytoreductive surgery in advanced epithelial ovarian cancer (EOC). Methods A total of 8 patients were recruited in this study who underwent partial pancreatectomy during the primary cytoreductive surgeries for advanced EOC in Fudan University Shanghai Cancer Center from April 2009 to July 2015. Their clinicopathological characteristics, diameter of metastatic tumors, the scope of cytoreductive surgeries, residual diseases after cytoreductive surgeries, postoperative complications and survival situation were retrospective analyzed. Results (1) Clinicopathological characteristics:the median age of these patients was 58 years old(range: 39-63 years old). The median value of preoperative serum CA125 was 1 688 kU/L(range: 119-5 000 kU/L). The median diameter of metastatic tumors involved in pancreatic body or tail was 4.5 cm (range:3-10 cm). All the tumors from the 8 patients were confirmed to be high-grade serous carcinoma. Four patients were staged as International Federation of Gynecology and Obstetrics (FIGO)Ⅳ, and the other 4 patients were staged as FIGOⅢc. (2) Tumor metastases and the scope of cytoreductive surgeries:all of these 8 patients had widely disseminated ovarian cancer, with involvement of upper abdominal, middle abdominal and pelvic cavity. Each patient underwent extensive intra-abdominal cytoreductive surgeries, including hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic periton-ectomy, splenectomy, partial pancreatectomy. Each patient had cytoreductive surgeries of 9.6 different sites on average. Of all 8 patients who underwent partial pancreatectomy, 7 patients had pancreatic tails removed;the other 1 patient had pancreatic body and tail removed. The median volume of blood loss during surgery was 1 350 ml(range:300-3 500 ml), blood transfusion was performed in 7 patients with the median volume of 1 150 ml (range: 500-1 800 ml). (3) Residual diseases after cytoreductive surgeries: optimal cytoreduction was achieved in all patients, with microscopic residual disease in 3 patients, residual tumors diameter < 0.5 cm in 3 patients, and residual tumors diameter between 0.5 and 1 cm in 2 patients. (4) Postoperative complications: 4 patients suffered from complications including pancreatic leakage (2/8), intraperitoneal hemorrhage (1/8) and pancreatic pseudocyst accompanied by infection (1/8). These complications were treated successfully by conservative managements. (5) Survival situation: during the median follow-up duration of 17 months (ranged from 2 to 46 months), 5 patients were still alive until the end of follow-up, including 4 cases under treatment and 1 case survived 29 months without relapse after treatment. Three patients were respectively died in 5, 20 and 46 months after surgery. Conclusion There is a higher risk of postoperative complications of pancreas resection as part of primary cytoreductive surgery in advanced epithelial ovarian cancer, but the resection of pancreatic metastases and part of the pancreas is feasible and necessary.
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Background and purpose:Gene fusions have been identiifed as recurrent oncogenic events in lung adenocarcinoma. Our purpose are to study the histologic features of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 receptor tyrosine kinase (ROS1) andRETproto-oncogene fusion-positive lung adenocarcinomas and to evaluate the correlation between psammoma bodies and fusion-positive lung adenocarcinomas.Methods:In this study, we performed a comprehensive histologic analysis of 44 fusion-positive (including 15RET, 20ALK and 9ROS1) lung adenocarcinomas and 111 fusion-negative [including 20 epidermal growth factor receptor (EGFR), 20 Kirsten rat sarcoma viral oncogene (K-ras), 71 pan-negative] lung adenocarcinomas.Results:ALK,RET andROS1 fusion-positive lung adenocarcinomas were more prevalent in solid or acinar predominant adenocarcinoma. Multivariate analysis showed that tumors harboring a fusion gene had significantly higher prevalence of the presence of signet ring cells (P=0.000), micropapillary component (P=0.044), mucinous cribriform pattern (P=0.000) and extracellular mucin (P=0.010). The incidence of psammoma bodies was higher in the lung adenocarcinomas with a gene fusion than in tumors without gene fusions (P=0.000). Psammoma bodies were more likely to be found in tumors with any micropapillary component and/or mucinous cribriform pattern than in tumors lacking a micropapillary component and/or mucinous cribriform pattern (P=0.000).Conclusion:Our data showed that the presence of psammoma bodies, micropapillary component, mucinous cribriform pattern, extracellular mucin or signet ring cells may be either sensitive or speciifc to predict tumors harboring a fusion gene. These distinct morphologic features may be helpful in selecting cases for further accurate molecular testing.
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Objective To investigate the appearance of solid papillary carcinoma (SPC)of breast on MRI and mammography correlated with histopathological features.Methods Fifteen patients with breast SPC diagnosed from January 2011 to January 2013 were enrolled.Their MR and mammography imaging findings were retrospectively reviewed,15 patients had MRI and 11 patients had mammography.The correlation between pathological characteristics and imaging findings was made.Results All the SPC displayed a solid-papillary growth pattern together with Luminal A type,and 14 cases showed neuroendocrine markers.On mammography,only three cases showed the abnormality.The most frequently seen MRI feature was its location in the posterior of areola (11 cases),ductal ectasia on T1WI (11 cases) and high signal intensity on T2WI.The enhancement patterns included non-mass-like enhancement (10 cases),mostly manifested as ductal with clumped enhancement (5 cases) and segmental with pebble shaped enhancement (4 cases),whereas mass-like enhancement (5 cases) exhibited as annular heterogeneous enhancement.Conclusions SPC is difficult to detect on mammography,but the MRI features may suggest its distinct histological type as papillary tumor.The ultimate diagnosis still depends on histopathology and immunohistochemical results.