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Background and Objective: Inflammatory myofibroblastic tumor (IMT) is a rare entity that is described in several organ systems. This comprehensive review aims to identify IMTs occurring at various genitourinary (GU) organ sites and describe patterns of clinical management in adult and pediatric patients. Methods: A comprehensive search of PubMed and Web of Science was conducted according to the Preferred Reporting Items for Systematic Review and meta-analyses statement. Two reviewers performed independent initial screening of abstracts. Eligible articles underwent full review and data extraction. The clinical features, diagnostic tests, treatment, and outcomes at each GU organ site were analyzed individually and summarized into a comprehensive review. Key Content and Findings: Of the 270 articles identified, 112 met inclusion criteria. Articles primarily consisted of case reports or small series describing a total of 167 cases, of which 30 (18%) occurred in children. Most patients (96%) were symptomatic at presentation. The most frequently involved sites included bladder (106 cases) and kidney (n=33) followed by epididymis (n=6), urachus (n=6), ureter (n=5), prostate (n=4), testis (n=4), and spermatic cord (n=3). Complete surgical excision of the mass including partial or total removal of involved organs provided excellent outcomes. Incomplete excision was associated with early local recurrence and progression. Late recurrence or metastatic transformation was rarely noted (<2%). Conclusions: IMTs exhibit locally invasive, symptomatic and progressive phenotypes that affect all urologic organs in adults and children. Clinical features and imaging results are similar to those noted with urologic cancers. These tumors require complete surgical excision since incomplete resection increases the risk of symptomatic recurrence.
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(1) Background: Acute myeloid leukemia (AML) accounts for up to one-third of more than 60,000 leukemia cases diagnosed annually in the U.S. Primary AML cells express membrane αvß3 integrin, which is associated with adverse prognosis and resistance to chemotherapies. A novel anticancer compound Polyethylene glycol-conjugated bi-TriAzole Tetraiodothyroacetic acid (P-bi-TAT) interacts with high affinity (Ki 0.3 nM) and specificity with the thyrointegrin αvß3. We evaluated P-bi-TAT activities in two different AML models representing monocytic and myelocytic forms of acute leukemia. (2) Methods and Results: The in vivo AML models were established prior to initiation of treatment protocols by grafting human leukemia cells in immunocompromised mice. IVIS imaging scans revealed that leukemic colonies were extensively established throughout the bone marrow, liver, and lung of the untreated animals. In animals treated with P-bi-TAT at daily doses ranging from 1-10 mg/kg, subcutaneously for 2-3 weeks, IVIS imaging scans revealed 95% reduction in bone marrow colonies and leukemic colonies in liver and lung. Also, the leukemic cells were not detected in bone marrow samples of P-bi-TAT-treated animals. The anti-neoplastic effect of P-bi-TAT administration on leukemic cells was associated with marked inhibition of NF-κB activity. We conclude that experimental P-bi-TAT therapy in vivo appears extraordinarily effective against the two forms of human AML models in mice. Because the P-bi-TAT molecular target, thyrointegrin αvß3, is consistently expressed in many, if not all, clinical AML samples, P-bi-TAT-based therapy seems to have significant clinical potential in treating most AML sub-types. Hence, P-bi-TAT represents a promising targeted therapeutic agent for AML patients.
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BACKGROUND: The association between Merkel cell carcinoma (MCC) and chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) is well established in the literature. A majority of MCCs are known to be associated with Merkel cell carcinoma polyomavirus (MCPyV), which is postulated to be a possible causative agent linking these two entities. We aim to identify the presence of MCPyV in patients with concurrent adjacent MCC and CLL/SLL. METHODS: Archived pathology materials of three cutaneous or surgical excisions with concurrent MCC and CLL/SLL were reviewed. Additional 12-µm sections from paraffin-embedded tissue of these resections were matched with original hematoxylin and eosin-stained slides and used to extract foci from each tumor separately. DNA was extracted from these tissues, and polymerase chain reaction (PCR), utilizing a primer set within a highly conserved "small T" viral DNA region, was done to detect MCPyV. RESULTS: Out of 140 cases of cutaneous or surgical excisions with MCC identified in our electronic medical records (EMR), three had coexisting neighboring CLL/SLL in the same resection specimen. In one case out of three, MCPyV was detected in MCC but not in CLL/SLL. The remaining two cases showed no detection of MCPyV in either MCC or CLL/SLL. CONCLUSION: MCPyV was not concurrently associated with adjacent MCC and CLL/SLL, indicating that it is not driving simultaneous tumorigenesis, at least in a subset of these cases.
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A 6-week-old female presented with gross hematuria and was diagnosed with Ewing sarcoma of the bladder through ultrasound and cystoscopic biopsies, along with a negative metastatic workup. She was treated with transurethral resection, chemotherapy consisting of with vincristine, cycolphosphamide, doxorubicin, ifosfamide and etoposide, and partial cystectomy. After completing chemotherapy, the patient has been doing well with no evidence of disease. There have been 14 other cases, 4 pediatric, of Ewing sarcoma of the bladder reported. To our knowledge, our case is the youngest patient reported with this disease.
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Neoplasias Ósseas/patologia , Sarcoma de Ewing/patologia , Neoplasias da Bexiga Urinária/secundário , Bexiga Urinária/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/terapia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Hematúria/diagnóstico , Humanos , Ifosfamida/uso terapêutico , Lactente , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/terapia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Vincristina/uso terapêuticoRESUMO
Inflammatory myofibroblastic tumors (IMT) of the urachus is a rare neoplastic condition characterized by proliferation of spindle cell, likely derived from myofibroblasts or fibroblasts, with acute and chronic inflammatory infiltrate. Urachal IMT present with abdominal/pelvic pain and urinary symptoms. These often manifest as abdominal mass involving adjacent structures. We describe a case of young female with urachal IMT that was excised with a wide margin to ensure complete removal of all adjacent affected tissue using robotic-assisted laparoscopic approach. Immunohistochemical evidence of ALK and ALK gene rearrangement were confirmed in this tumor which are diagnostic of IMT.
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Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features.131 pathologists with genitourinary expertise were invited in an online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up.Fifty (38%) participants completed the survey. 46 of 50 participants reported multiple patterns, most commonly papillary pattern (almost always 9/46, 19.5%; frequently 29/46, 63%). Large epithelioid cells with abundant cytoplasm were the most encountered cytologic feature, with either clear (almost always 10/50, 20%; frequently 34/50, 68%) or eosinophilic (almost always 4/49, 8%; frequently 28/49, 57%) cytology. Strong (3+) or diffuse (>75% of tumour cells) nuclear TFE3 IHC expression was considered diagnostic by 13/46 (28%) and 12/47 (26%) participants, respectively. Main TFE3 IHC issues were the low specificity (16/42, 38%), unreliable staining performance (15/42, 36%) and background staining (12/42, 29%). Most preferred IHC assays other than TFE3, cathepsin K and pancytokeratin were melan A (44/50, 88%), HMB45 (43/50, 86%), carbonic anhydrase IX (41/50, 82%) and CK7 (32/50, 64%). Cut-off for positive TFE3 fluorescent in situ hybridisation (FISH) was preferably 10% (9/50, 18%), although significant variation in cut-off values was present. 23/48 (48%) participants required TFE3 FISH testing to confirm TFE3-RCC regardless of the histomorphologic and IHC assessment. 28/50 (56%) participants would request additional molecular studies other than FISH assay in selected cases, whereas 3/50 participants use additional molecular cases in all cases when TFE3-RCC is in the differential.Optimal diagnostic approach on TFE3-RCC is impacted by IHC and/or FISH assay preferences as well as their conflicting interpretation methods.
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/diagnóstico , Rearranjo Gênico , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Renais/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/química , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Pesquisas sobre Atenção à Saúde , Humanos , Lactente , Neoplasias Renais/química , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Patologistas , Fenótipo , Padrões de Prática Médica , Valor Preditivo dos Testes , Adulto JovemRESUMO
Purpose: Due to improved survival durations and enhanced surveillance modalities, metastases of systemic malignancies to the orbit are increasing. This review is intended to discuss the epidemiologic, clinical, and management features of orbital metastases. Methods: A literature search for relevant publications on the topic was performed via PubMed, and the appropriate data were extracted from these manuscripts. Results: While rare, metastases to the orbit are regularly encountered in clinical practice. The overwhelming majority of these lesions present in adult patients, and metastatic disease may emerge several years after the diagnosis of the initial cancer. Subjectively, these lesions tend to present with complaints of diplopia, blurred vision, and pain, and objective signs tended to include vision loss, limitation of extraocular motility, proptosis, the presence of a palpable mass, and ptosis. Different studies reported a variety of primary tumors, although breast and lung malignancies were generally among the most common. A sizeable portion of patients may not have a known primary malignancy. After detection, survival rates are generally short, and metastatic disease suggests a worrisome prognosis. Radiation therapy may alleviate symptoms. Conclusions: Metastases of systemic disease present with specific subjective, clinical, and radiographic features. Furthermore, these lesions may present years after an initial diagnosis. Clinicians should be aware of the implications of this malady on patient survival and must consider interventions to improve quality of life.
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Exoftalmia , Neoplasias Orbitárias , Adulto , Diplopia , Humanos , Órbita , Neoplasias Orbitárias/terapia , Qualidade de VidaRESUMO
Hepatoblastoma (HBL) is a hepatic malignancy of infants and young children, which is often cured by combinations of surgery and chemotherapy. Management of refractory and metastatic HBL is challenging. Comprehensive genomic profiling was performed on 31 refractory and metastatic HBL using a hybrid-capture, adaptor ligation-based next-generation sequencing assay. Tumor mutation burden (TMB) was calculated from a minimum of 1.11 Mb of sequenced DNA and reported as mutations/Mb. The results were analyzed for all classes of genomic alterations (GA). Activating CTNNB1 mutation was the most frequent GA seen in 19 (61%) of cases. All 3 (100%) mixed epithelial and mesenchymal HBL harbored CTNNB1 mutation. The small cell undifferentiated subtype showed SMARCB1 loss in both cases. There was no significant further correlation of GA with histologic subtype. In addition to the potential targeting of CTNNB1, other rarely identified possible targetable GA included ERBB4 (6%) and FBXW7, SRC and BRCA2 (each at 3%). The mean TMB was 3.5 mut/Mb, the median was 1.7 mut/Mb. There were 2 HBL with ≥10 mut/Mb. No alterations in TP53 were identified, and alterations in the DNA repair pathways were rare. Refractory and metastatic HBL is characterized by a general paucity of GA and is dominated by frequent CTNNB1 mutation and overall low TMB. Although potentially targetable GA are seen on occasion in HBL and a small number of cases have high TMB with potential to respond to immune checkpoint inhibitors, advanced HBL will remain a treatment challenge.
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Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Variação Genética , Hepatoblastoma/genética , Neoplasias Hepáticas/genética , Mutação , Adolescente , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Análise Mutacional de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Predisposição Genética para Doença , Hepatoblastoma/tratamento farmacológico , Hepatoblastoma/secundário , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Terapia de Alvo Molecular , Fenótipo , Medicina de Precisão , Valor Preditivo dos TestesRESUMO
BACKGROUND: In the current study, the authors present a comprehensive genomic profile (CGP)-based study of advanced urothelial carcinoma (UC) designed to detect clinically relevant genomic alterations (CRGAs). METHODS: DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections from 295 consecutive cases of recurrent/metastatic UC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 688X for all coding exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer, using process-matched normal control samples as a reference. CRGAs were defined as GAs linked to drugs on the market or currently under evaluation in mechanism-driven clinical trials. RESULTS: All 295 patients assessed were classified with high-grade (International Society of Urological Pathology classification) and advanced stage (stage III/IV American Joint Committee on Cancer) disease, and 294 of 295 patients (99.7%) had at least 1 GA on CGP with a mean of 6.4 GAs per UC (61% substitutions/insertions/deletions, 37% copy number alterations, and 2% fusions). Furthermore, 275 patients (93%) had at least 1 CRGA involving 75 individual genes with a mean of 2.6 CRGAs per UC. The most common CRGAs involved cyclin-dependent kinase inhibitor 2A (CDKN2A) (34%), fibroblast growth factor receptor 3 (FGFR3) (21%), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (20%), and ERBB2 (17%). FGFR3 GAs were diverse types and included 10% fusions. ERBB2 GAs were equally divided between amplifications and substitutions. ERBB2 substitutions were predominantly within the extracellular domain and were highly enriched in patients with micropapillary UC (38% of 32 cases vs 5% of 263 nonmicropapillary UC cases; P<.0001). CONCLUSIONS: Using a CGP assay capable of detecting all classes of GA simultaneously, an extraordinarily high frequency of CRGA was identified in a large series of patients with advanced UC. Cancer 2016;122:702-711. © 2015 American Cancer Society.
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Carcinoma de Células de Transição/genética , Variação Genética/genética , Recidiva Local de Neoplasia/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/secundário , Classe I de Fosfatidilinositol 3-Quinases , Bases de Dados Factuais , Feminino , Amplificação de Genes , Deleção de Genes , Fusão Gênica , Rearranjo Gênico , Genes erbB-2 , Genes p16 , Genes p53 , Humanos , Masculino , Mutação , Metástase Neoplásica/genética , Recidiva Local de Neoplasia/patologia , Fosfatidilinositol 3-Quinases/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
Sulfated non-anticoagulant heparins (S-NACHs) might be preferred for potential clinical use in cancer patients without affecting hemostasis as compared to low molecular weight heparins (LMWHs). We investigated anti-tumor effects, anti-angiogenesis effects, and mechanisms of S-NACH in a mouse model of pancreatic cancer as compared to the LMWH tinzaparin. S-NACH or tinzaparin with or without gemcitabine were administered, and tumor luminescent signal intensity, tumor weight, and histopathology were assessed at the termination of the study. S-NACH and LMWH efficiently inhibited tumor growth and metastasis, without any observed bleeding events with S-NACH as compared to tinzaparin. S-NACH distinctly increased tumor necrosis and enhanced gemcitabine response in the mouse pancreatic cancer models. These data suggest the potential implication of S-NACH as a neoadjuvant in pancreatic cancer.
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Inibidores da Angiogênese/farmacologia , Fibrinolíticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Camundongos , Camundongos Nus , Metástase Neoplásica , Neovascularização Patológica/tratamento farmacológico , Tinzaparina , Ensaios Antitumorais Modelo de Xenoenxerto , GencitabinaRESUMO
Although urothelial carcinoma (UC) of the urinary bladder generally portends a favorable prognosis, metastatic tumors often follow an aggressive clinical course. DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded (FFPE) sections from 35 stage IV UCs that had relapsed and progressed after primary surgery and conventional chemotherapy. Next-generation sequencing (NGS) was performed on hybridization-captured, adaptor ligation-based libraries for 3320 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer to at an average sequencing depth of 1164 × and evaluated for all classes of genomic alterations (GAs). Actionable GAs were defined as those impacting the selection of targeted anticancer therapies on the market or in registered clinical trials. A total of 139 GAs were identified, with an average of 4.0 GAs per tumor (range 0-10), of which 78 (56%) were considered actionable, with an average of 2.2 per tumor (range 0-7). Twenty-nine (83%) cases harbored at least one actionable GA including: PIK3CA (9 cases; 26%); CDKN2A/B (8 cases; 23%); CCND1 (5 cases; 14%); FGFR1 (5 cases; 14%); CCND3 (4 cases; 11%); FGFR3 (4 cases; 11%); MCL1 (4 cases; 11%); MDM2 (4 cases; 11%); EGFR (2 cases, 6%); ERBB2 (HER2/neu) (2 cases, 6%); NF1 (2 cases, 6%) and TSC1 (2 cases, 6%). Notable additional alterations included TP53 (19 cases, 54%) and RB1 (6 cases; 17%). Genes involved in chromatin modification were altered by nonsense mutation, splice site mutation or frameshift indel in a mutually exclusive manner in nearly half of all cases including KDM6A (10 cases; 29%) and ARID1A (7 cases; 20%). Comprehensive NGS of 35 UCs of the bladder revealed a diverse spectrum of actionable GAs in 83% of cases, which has the potential to inform treatment decisions for patients with relapsed and metastatic disease.
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Carcinoma de Células de Transição/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNARESUMO
PURPOSE: Micropapillary urothelial carcinoma (MPUC) is a rare and aggressive form of bladder cancer. We conducted genomic analyses [next-generation sequencing (NGS)] of MPUC and non-micropapillary urothelial bladder carcinomas (non-MPUC) to characterize the genomic landscape and identify targeted treatment options. EXPERIMENTAL DESIGN: DNA was extracted from 40 µm of formalin-fixed paraffin-embedded sections from 15 MPUC and 64 non-MPUC tumors. Sequencing (NGS) was performed on hybridization-captured, adaptor ligation-based libraries to high coverage for 3,230 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. The results were evaluated for all classes of genomic alteration. RESULTS: Mutations in the extracellular domain of ERBB2 were identified in 6 of 15 (40%) of MPUC: S310F (four cases), S310Y (one case), and R157W (one case). All six cases of MPUC with ERBB2 mutation were negative for ERBB2 amplification and Erbb2 overexpression. In contrast, 6 of 64 (9.4%) non-MPUC harbored an ERBB2 alteration, including base substitution (three cases), amplification (two cases), and gene fusion (one case), which is higher than the 2 of 159 (1.3%) protein-changing ERBB2 mutations reported for urinary tract cancer in COSMIC. The enrichment of ERBB2 alterations in MPUC compared with non-MPUC is significant both between this series (P < 0.0084) and for all types of urinary tract cancer in COSMIC (P < 0.001). CONCLUSIONS: NGS of MPUC revealed a high incidence of mutation in the extracellular domain of ERBB2, a gene for which there are five approved targeted therapies. NGS can identify genomic alteration, which inform treatment options for the majority of MPUC patients.
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Receptor ErbB-2/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Estrutura Terciária de Proteína , Análise de Sequência de DNARESUMO
Urothelial carcinoma (UC) of the renal pelvis has been rarely shown to metastasize to the skin. Tumor seeding from iatrogenic procedures is a source of spreading of UC to the skin. We herein present a case of primary UC of the renal pelvis with spreading to the skin from a percutaneous nephrostomy tract.
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Spinal primary dural lymphoma (PDL) is uncommon with a total of 37 previous well-documented cases reported, including one diagnosed in the authors' institution. More recently we encountered an additional case of spinal PDL that, similarly to our previous case, was grade 1-2 follicular B-cell PDL. Our two cases were diagnosed over a 3-year interval in a 72-year-old female and a 74-year-old male, respectively. An exhaustive literature review on PDL was performed consequently to reveal that: (i) spinal and cerebral sites of involvement by PDL are constantly mutually exclusive; and (ii) unlike cerebral PDL, which is usually of marginal zone B-cell type, only two of the 38 cases of spinal PDL were diagnosed as such, diffuse large B-cell lymphoma being the most commonly encountered type in the spine. This divergence infers that, in contrast to the prevailing concept that PDL is a unique disease group, PDL appears to be rather heterogeneous with a difference in predilection of lymphoma type for the anatomical site of dural involvement. Such a site-specific lymphoma-type predilection phenomenon, well-recognized in other organ systems, has not been acknowledged in PDL. This report brings new insights into PDL, and may contribute to a better understanding of nervous system pathophysiology and lymphoma classification.
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Dura-Máter/patologia , Linfoma de Células B/patologia , Linfoma Folicular/patologia , Neoplasias Meníngeas/patologia , Neoplasias da Coluna Vertebral/patologia , Idoso , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Linfoma de Células B/terapia , Linfoma Folicular/terapia , Masculino , Neoplasias Meníngeas/terapia , Neoplasias da Coluna Vertebral/terapia , Resultado do TratamentoRESUMO
Histopathologic findings of gonadal torsion in neonates and infants (GTNI) are poorly defined in the literature. We describe herein the histopathologic spectrum of GT with emphasis on the pediatric population and on features specific for NI (≤1 year of age). Twenty-four cases of GTNI (6 females/18 males), 33 cases of GT in an older pediatric population (OPP) (19 females/14 males), and 43 cases of GT in adults (35 females/8 males) were found in our pathology files between 2003 and 2011. Our findings disclosed 2 categories of GT: 1) the group of NI, and 2) that of OPP and adults who share a similar presentation as acute hemorrhagic necrosis of the gonad. Although findings in NI were rather uniform, a few differences were demonstrated between the 2 genders. All GTNI revealed calcifications, fibrosis, siderophages, and extensive necrosis. However, prominent necrotizing palisaded granulomatas were seen in most (4 of 6) cases of ovarian torsion but not in the testicular counterpart. Furthermore, complete gonad regression was encountered exclusively in neonatal testicular torsion cases. In conclusion, 1) pathologic findings in GT are distinctly different between NI and OPP, the latter being more comparable to adults, presenting with acute hemorrhagic necrosis; 2) the distinctive findings in GTNI of both genders include calcifications, siderophages, and fibrosis, in addition to background necrosis; 3) of particular note, complete gonadal regression is seen only in the testis in GTNI; and 4) necrotizing palisaded granulomatas are unique to the ovarian subgroup and are often extensive, obscuring the nature of the process.
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Transtornos Gonadais/patologia , Anormalidade Torcional/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Gônadas , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
A micropapillary variant of prostatic acinar adenocarcinoma has not been reported in the literature. Herein, we report a case of a 50-year-old patient who presented with an elevated prostate-specific antigen concentration and was subsequently diagnosed with prostatic acinar adenocarcinoma on biopsy. Radical prostatectomy specimen revealed prostatic carcinoma with Gleason score 4 + 5 â=â 9/10, with micropapillary component constituting 80% of tumor volume. Immunohistochemical studies of the prostate carcinoma showed a homogeneously positive prostate-specific antigen and α-methylacyl-CoA racemase, high-molecular-weight cytokeratin, and p63 protein cocktail pattern of staining in both micropapillary and conventional components. Pelvic lymph nodes were negative for metastatic disease. In contrast to the aggressive behavior of micropapillary carcinomas of other organs, the disease in our patient has thus far followed a more benign course, with low stage on presentation and a 2-year follow-up free of disease. However, prognostic correlation should be established on large series in order to assign this variant to a grade category within the Gleason scheme.
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Adenocarcinoma Papilar/patologia , Carcinoma de Células Acinares/patologia , Neoplasias da Próstata/patologia , Adenocarcinoma Papilar/metabolismo , Carcinoma de Células Acinares/metabolismo , Humanos , Imuno-Histoquímica , Queratinas/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Racemases e Epimerases/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
PURPOSE: A prior investigation has demonstrated that innate immune-specific cytokines are enriched in idiopathic orbital inflammation (IOI). To further document the role of innate immunity in IOI, the authors sought to determine whether toll-like receptors (TLRs) are present in biopsy specimens of this disorder. METHODS: Immunohistochemical staining for TLR2, TLR3, and TLR4 was performed on biopsy specimens taken from patients with IOI, and the number of TLR-positive cells was counted across five 40× light microscopic fields. These results were compared with an isotype control and with orbital adipose tissue taken from patients without evidence of inflammation. RESULTS: All IOI specimens demonstrated positivity for all 3 TLRs, and sections stained for isotype controls did not demonstrate any positivity. Furthermore, orbital adipose tissue did not demonstrate any significant signal. The mean number of positive cells was 24.4 cells/high power field (hpf; standard deviation = 11.6 cells/hpf), 7.23 cells/hpf (standard deviation = 5.59 cells/hpf), and 11.7 cells/hpf for TLR2, TLR3, and TLR4, respectively. CONCLUSIONS: This study provides the first documentation of TLRs in orbital disease. Toll-like receptors are present in IOI, and IOI may represent an aberrant innate immune response. Interference with TLRs may represent an additional potential therapeutic mechanism in the management of IOI.
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Pseudotumor Orbitário/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 3 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Tecido Adiposo/metabolismo , Adulto , Biópsia , Blefaroplastia , Humanos , Imunidade Inata , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Pseudotumor Orbitário/imunologia , Pseudotumor Orbitário/patologia , Estudos RetrospectivosRESUMO
The purpose of this study was to determine the activity of topotecan given by 21-day continuous infusion in patients previously treated with one prior therapy for a diffuse large-cell lymphoma or immunoblastic lymphoma. Patients with appropriate histology and measurable disease who had been treated with one prior chemotherapy regimen were eligible for study. Slides of tumor biopsies were submitted for central review of pathology. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 and adequate bone marrow function. Patients were treated with continuous infusion topotecan, 0.4 mg/m(2)/day × 21 days. Therapy could be escalated to 0.5 and then 0.6 mg/m(2)/day in subsequent cycles if there was no dose-limiting toxicity at the initial dose level. Patients were treated with two cycles after achieving a complete response or until disease progression or unacceptable toxicity occurred. Thirty-seven patients were enrolled. However, only 26 cases were eligible due to a performance status of > 2 (n = 2), more than one prior chemotherapy (n = 1) and wrong histology on review (n = 8). Due to the unexpectedly high ineligibility rate, two sets of analysis were done for all 37 patients enrolled and for the 26 eligible patients, respectively. Of the 37 patients (15 males and 22 females), the International Prognostic Index included 11% low risk, 30% low intermediate risk, 46% high intermediate risk and 8% high risk. The median follow-up was 77 months. A total of 136 cycles of therapy were given with a median of 3 cycles per patient. Grade 4 toxicities included: 14% grade 4 thrombocytopenia; 14% grade 4 granulocytopenia, 8% leukopenia, 3% each anemia, hemorrhage, infection, vomiting, thrombosis, liver toxicity and neuromotor toxicity. The response analysis including all 37 patients showed five complete responses (CRs) and four partial responses (PRs) for a total response rate of 24% (90% two-stage confidence interval 13-39%). Median progression-free survival (PFS) was 3.7 months, with 1- and 2-year PFS of 21% and 6%, respectively (90% confidence interval 11-34% and 2-15%). Median overall survival (OS) was 10.5 months, with 1- and 2-year OS of 41% and 27%, respectively (90% confidence interval 27-53% and 16-39%). Analysis including only eligible patients showed similar response rates and survival outcomes. Single agent topotecan has moderate activity for previously treated high-grade lymphoma equivalent to that of several newer agents, and should be considered for incorporation into multi-drug salvage chemotherapy programs.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Topotecan/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Seguimentos , Humanos , Bombas de Infusão , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Oncologia/organização & administração , Pessoa de Meia-Idade , Estudos Retrospectivos , Sociedades Médicas/organização & administração , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
We report a case of an extra nuchal-type fibroma in a 51-year-old male suspected to have attenuated familial adenomatous polyposis (Gardner's syndrome), who presented with a longstanding buttock mass excised due to enlargement and pain. Histopathologically, lobules of haphazard, hypocellular, hyalinized collagen bundles replaced the dermis and subcutis and entrapped nerve bundles, mimicking Morton neuroma. Ramifying nerve twigs found around larger nerve fascicles showed the co-existence of traumatic neuroma. Elastic tissue stain revealed elastosis characterized by large, arborizing fibers lying between and within the hyalinized collagen bundles. Modified Masson's trichrome stain showed light blue staining of collagen bundles producing the hyalinized nodules with irregular, light red staining of collagen bundles at their periphery and within tumor collagen. Compression and/or degeneration of collagen and secondary elastosis with later entrapment by tumor collagen could explain this microscopic phenotype. By immunohistochemistry, tumor spindle cells expressed nuclear ß-catenin and cyclin D1, mostly within regions of fibrosis implicating activation of the adenomatous polyposis coli (APC)-Wnt pathway. Genetic analysis showed a missense mutation in APC gene (c.7504G>A, p.G2502S in exon 15) and a functional homozygous polymorphism in the MUTYH gene (c.36+325G>C, (IVS1+5G/C)). Nuchal-type fibroma has been associated with Gardner's syndrome and trauma. In this patient, genetic predisposition coupled with repetitive, localized trauma and collagen degeneration may have provided the stimulus for the development of extra nuchal-type fibroma.
Assuntos
DNA Glicosilases/genética , Dermatoses Faciais/patologia , Fibroma/patologia , Genes APC , Mutação de Sentido Incorreto , Neuroma/patologia , Polimorfismo Genético , Neoplasias de Tecidos Moles/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , DNA Glicosilases/metabolismo , Dermatoses Faciais/genética , Dermatoses Faciais/cirurgia , Fibroma/genética , Fibroma/cirurgia , Síndrome de Gardner/diagnóstico , Síndrome de Gardner/genética , Síndrome de Gardner/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma/genética , Neuroma/cirurgia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/cirurgiaRESUMO
OBJECTIVE: Detection of large cell transformation (LCT) has been reported with the increasing use of PET/computed tomography (CT) in patients with indolent lymphomas. However, there is little information on PET/CT characteristics, specifically, the distribution of lesion maximum standardized uptake value (SUV(max)) within a patient, or SUV(max) changes before and after LCT. Our objectives were to compare SUV(max) values and distribution between nontransformed and LCT patients; to compare SUV(max) of LCT and nontransformed lesions in patients with documented focal transformation; and to measure the SUV(max) changes in patients before and after LCT. METHODS: Retrospective study of patients with LCT (n=29)compared with nontransformed (n=41), and comparison of LCT and nontransformed lesions within patients and over time. RESULTS: On average, the highest SUV(max) was greater in LCT patients than in nontransformed patients. In addition, there was a wider range of SUV(max) values in the LCT group compared with the nontransformed group (P<0.05). The median ratio of the SUV(max) of 12 LCT to nontransformed biopsy-proven lesions in the same patient was 4.3, P value of less than 0.05 (range 2.6-15.5). In 10 of 12 patients it was greater than or equal to 3. No change in highest SUV(max) and distribution was shown on serial PET in untreated nontransformed patients. CONCLUSION: LCT is often focal and is associated with higher SUV(max) than nontransformed. The emergence of a focus with SUV(max) three times or higher than others on a single scan, or that has tripled or more in value on serial scans, should raise suspicion for LCT.