Botucatu, Brazil
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Falconieri G.,General Hospital S Maria Della Misericordia | Bacchi C.E.,Consultoria em Patologia | Luzar B.,University of Ljubljana
American Journal of Dermatopathology | Year: 2012

Clear cell sarcoma is a unique soft tissue tumor with distinct microscopic features that include a nested or fascicular pattern of spindle cells accompanied by larger wreath-like giant cells scattered throughout. It harbors a unique EWSR1-ATF1 gene fusion secondary to a t(12;22)(q13;q12) translocation. Recently, it was reported that clear cell sarcoma can occur in the skin and mimic a broad spectrum of entities, including spindle cell melanoma. Here, we describe 3 new cases of clear cell sarcoma of the skin, all of which were confirmed molecularly. The patients, a 12-year-old boy, a 29-year-old woman, and a 60-year-old man, had cutaneous lesions on the thigh, dorsum of foot, and sole, respectively. All 3 lesions were originally considered suspicious of spindle cell melanoma. Microscopically, the lesions featured nodular proliferation centered in the dermis that consisted of discrete fascicles of spindle cell enmeshed by thin fibrous strands. Wreath-like cells were present in all cases. Tumor cells were positive for S100 protein (3 of 3 cases), melan A (2 of 3 cases), HMB 45 (1 of 3 cases) although a junctional melanocytic proliferation was seen in 1 case. Sentinel lymph node biopsy was negative in 2 patients. Follow-up was uneventful in 2 patients, whereas the other patient developed a lymph node metastasis 5 months after primary tumor excision. This study confirms that malignant dermal tumors that mimic but do not exactly replicate spindle cell melanoma should raise suspicion for cutaneous clear cell sarcoma and prompt the investigation for the confirmatory gene fusion t(12;22). © 2012 by Lippincott Williams & Wilkins.


Salviato T.,General Hospital S Maria Degli Angeli | Bacchi C.E.,Consultoria em Patologia | Luzar B.,University of Ljubljana | Falconieri G.,University of Udine
American Journal of Dermatopathology | Year: 2013

We report 2 cases of cutaneous epithelioid angiosarcoma featuring predominantly signet ring cells. The patients-a woman, 68 years of age, and a man, 85 years of age, respectively-were referred for slowly growing indurated plaques on their parietal and retroauricular skin. Microscopic examination showed diffuse dermal proliferations comprising polygonal cells and relatively abundant cytoplasm. Because the tumor cells often were distended by variably sized vacuoles pushing the nuclei to the periphery, the nuclear profile tended toward a crescent-like morphology. Abortive luminal formations were recognized. The tumor cells were positive for CD31, CD34, and D2-40/podoplanin, with no expression of epithelial or melanocytic markers. In 1 case, upon ultrastructural examination of paraffin-embedded tissue-cut from wax tissue and reprocessed-the optically empty spaces were surrounded by a membrane with ultrastructural features identical to those of the outer cell membrane, suggesting that these spaces corresponded to the formation of primitive intracytoplasmic lumina within the tumor cells. A few Weibel-Palade bodies also were noted. Our report offers further evidence that epithelioid angiosarcoma of the skin has a broad microscopic spectrum and that tumors displaying a preponderant population of signet ring cells pose further diagnostic challenges. A brief overview of cutaneous malignant tumors in the differential diagnosis of signet ring cell angiosarcoma is provided. © 2013 Lippincott Williams &Wilkins.


Chisholm K.M.,Stanford University | Chisholm K.M.,Boston Childrens Hospital | Bangs C.D.,Stanford University | Bacchi C.E.,Consultoria em Patologia | And 3 more authors.
American Journal of Surgical Pathology | Year: 2015

MYC translocations are a defining feature of Burkitt lymphoma and a group of diffuse large B-cell lymphoma (DLBCL) with inferior outcome. However, the clinical relevance of MYC gene rearrangement and its relationship with MYC protein expression has not been well characterized in lymphomas. Tissue microarrays containing 1214 lymphomas were successfully evaluated by immunohistochemistry using anti-MYC clone Y69 and a dual-color break-apart fluorescence in situ hybridization probe to detect MYC gene rearrangements. Aggressive B-cell lymphomas including Burkitt lymphoma and DLBCL showed the highest level of MYC protein staining defined as staining in >50% of lymphoma cells. A significant proportion of plasmablastic, B-lymphoblastic and T-lymphoblastic, and extranodal NK/T-cell lymphomas also showed staining in >50% of cells, whereas only occasional plasma cell myeloma, mantle cell lymphoma, and classical Hodgkin lymphoma showed a high level of staining. Small B-cell lymphomas, when positive, showed MYC protein in <50% of cells. In aggressive B-cell lymphomas, MYC rearrangement and MYC immunohistochemistry showed a high concordance rate; however, some DLBCL and all T-cell and NK-cell lymphomas with MYC protein expression lacked MYC gene rearrangements. Our results provide a baseline for MYC protein expression in lymphomas and indicate that its expression is not specific to lymphoma subtypes, cell lineage, or expected clinical behavior and is highly variable. In addition, MYC protein expression is not necessarily correlated with MYC gene rearrangements and suggests the need for caution in the interpretation of MYC immunohistochemistry in the differential diagnosis of lymphomas. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Weiss L.M.,City of Hope National Medical Center | Bacchi C.E.,Consultoria em Patologia
Applied Immunohistochemistry and Molecular Morphology | Year: 2010

The identification of monotypic light chains is an important adjunct to the diagnosis of B-cell lymphoma, yet to reliably perform it on formalin-fixed paraffin sections is often difficult. We have evaluated a new set of monoclonal antibodies to κ and λ light chains that are reactive in paraffin sections. In reactive lymphoid tissues, polytypic staining was noted in greater than 95% of cases, with strong staining of plasma cells, moderate staining of the follicular dendritic cell network, and weak staining of mantle zone cells. Strong staining of the appropriate light chain was seen in each of the 7 cases of multiple myeloma. In a series of 58 cases of B-cell lymphoma, correlation between the results of immunohistochemistry and flow cytometry was obtained in 36 cases (62%), including 32 cases (21 κ and 11 λ) in which a single light chain was expressed. Monotypic staining was also seen in 6 additional cases (10%) in which flow cytometry was negative. Thirty of 46 cases (65%) of follicular lymphoma showed monotypic light chain expression, in contrast to 64 of 67 cases (95%) of reactive lymphoid hyperplasia, which showed polytypic light chain expression. These antibodies may provide an effective adjunct to the diagnosis of B-cell lymphoma in routine diagnostic work. Copyright © 2010 by Lippincott Williams & Wilkins.


Gualco G.,Consultoria em Patologia | Weiss L.M.,City of Hope National Medical Center | Bacchi C.E.,Consultoria em Patologia
Applied Immunohistochemistry and Molecular Morphology | Year: 2010

MUM1/IRF4 protein is a member of the interferon regulatory factor (IRF) family of transcriptional factors initially described as downstream regulators of interferon signaling. The quantity of this factor varies within the hematopoietic system in a lineage and stage-specific way. It is considered to be a key regulator of several steps in lymphoid, myeloid, and dendritic cell differentiation and maturation. MUM1/IRF4 expression is observed in many lymphoid and myeloid malignancies, and may be a promising target for the treatment of some of these neoplasms. We reviewed the literature on MUM1/IRF4, with emphasis on the pathologic aspects of this marker in reactive and malignant hematologic and nonhematologic conditions. © 2010 by Lippincott Williams & Wilkins.


Lopes L.F.,Consultoria em Patologia | Bacchi C.E.,Consultoria em Patologia
Journal of Cellular and Molecular Medicine | Year: 2010

Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins. © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.


Gualco G.,Consultoria em Patologia | Domeny-Duarte P.,Consultoria em Patologia | Chioato L.,Consultoria em Patologia | Barber G.,University of Miami | And 2 more authors.
American Journal of Surgical Pathology | Year: 2011

Extranodal natural killer/T-cell lymphoma, nasal type (NK/TCL) is more prevalent in Asia and in some areas of South and Central America, but it is rarely seen in the United States and Europe. In this study, a series of 122 cases of NK/TCL from Brazil was analyzed with respect to clinicopathologic features. Clinical characteristics and geographic distribution were evaluated in 97 cases of nasal/nasopharyngeal region and 23 cases in extranasal sites including 6 nodal cases. Clinical staging and follow-up information was available in a subset of 21 patients. All cases harbored Epstein-Barr virus (EBV), 95% and 85% expressed cytoplasmic CD3 and CD56, respectively, and all cases were positive for at least 1 marker for cytotoxic granules. The global distribution of EBV subtypes showed predominance of strain subtype A, 89%, and subtype B, 11%. No dual infections were detected. TCR-γ TCR-gene rearrangement was observed in 7 cases; all of them extranodal. Three of TCR-γ+ cases showed EBV subtype A. Two TCR-γ+/ CD56+ cases showed EBV subtype B. Geographic distribution of NK/TCL showed higher frequency in the southeast and northeast regions of Brazil. Striking differences among geographic regions were seen with the vast majority of EBV subtype B (86%) occurring in the south and southeast regions. Copyright © 2011 by Lippincott Williams & Wilkins.


Estrozi B.,Consultoria em Patologia | Bacchi C.E.,Consultoria em Patologia
Clinics | Year: 2011

OBJECTIVE: Description of some of the clinical pathological characteristics of neuroendocrine tumors of the gastroenteropancreatic tract in Brazilian patients. INTRODUCTION: Neuroendocrine tumors arise in many organs and share common pathological features. In 2010, the World Health Organization published a new classification for neuroendocrine tumors using a three-tiered system that applies the terms neuroendocrine tumor Grade 1, neuroendocrine tumor Grade 2, and neuroendocrine carcinoma. The tumor grades are based on their mitotic rate and the Ki-67 index. In Brazil, information on neuroendocrine tumors of gastroenteropancreatic tract is scarce. METHODS: This study investigated clinicopathological features of 773 Brazilian gastroenteropancreatic neuroendocrine tumor cases from all the geographic regions of Brazil. All of the cases emerged from the files of a single institution (a large pathology reference laboratory) between 1997 and 2009. In addition, the gastroenteropancreatic neuroendocrine tumors were graded according to the new 2010 World Health Organization classification. RESULTS: Overall there were a higher number of neuroendocrine tumors in female over male. The lower ages were seen in patients with appendiceal tumors. The most common anatomic location involved was stomach followed by small and large intestines. All cases involving the appendix were of grade 1 and 92.1% of the neuroendocrine tumors of the esophagus were neuroendocrine carcinomas (grade 3). CONCLUSIONS: In this series, the proportion of NET cases in the total number of surgical pathology cases at our institution over the past 12 years is increasing. © 2011 CLINICS.


Lopes L.F.,Consultoria em Patologia | Bacchi C.E.,Consultoria em Patologia
Applied Immunohistochemistry and Molecular Morphology | Year: 2012

Gastrointestinal stromal tumor is the most common clinically significant mesenchymal neoplasm of the gastrointestinal tract. The expression of the intermediate filament cytokeratin in gastrointestinal stromal tumor is not frequently reported in the literature. The aim of this study was to investigate the immunohistochemical expression of several types of cytokeratin in a large number of cases (n=687), including a pan-cytokeratin marker (AE1/AE3 cocktail antibodies), high-molecular weight cytokeratins (34ßE12 antibody), and individual cytokeratins 8 (35ßH11 and CAM5.2 antibodies), 7, 14, and 20. Ki-67 antigen was used for the determination of cell proliferation index, and the correlation between Ki-67 and cytokeratin expression was evaluated. Cytokeratin expression was also correlated with several clinicopathologic parameters. The expression of pan-cytokeratin was observed in 24 (3.5%) cases, with variable intensity. Only 1 of 687 (0.1%) cases showed cytokeratin 14 expression. All 687 cases revealed no expression of high-molecular weight cytokeratins, cytokeratins 7, 8, and 20. No significant statistical association was found between AE1/AE3 immunoreactivity and several clinicopathologic parameters, including sex, tumor location and size, cell morphology, mitotic count, risk of aggressive behavior, and Ki-67 antigen cell proliferation index. However, statistical correlation between AE1/AE3 immunoreactivity and a higher age at diagnosis was detected. These results show that cytokeratin expression is not frequent in gastrointestinal stromal tumor, but caution is necessary to avoid erroneous diagnoses. © 2012 by Lippincott Williams & Wilkins.


Gualco G.,Consultoria em Patologia | Natkunam Y.,Stanford University | Bacchi C.E.,Consultoria em Patologia
Modern Pathology | Year: 2012

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, is a diagnostic provisional category in the World Health Organization (WHO) 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typically, these cases share features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this study, we present 10 cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma and have organized the criteria described by the WHO into four patterns along with detailed clinical, morphological and immunophenotypic characterization and outcome data. Our findings show a male preponderance, median age of 37 years and a mediastinal presentation in 80% of cases. All cases expressed at least two markers associated with B-cell lineage and good response to combination chemotherapy currently employed for non-Hodgkin lymphomas. © 2012 USCAP, Inc. All rights reserved.

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