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1.
Cureus ; 15(11): e49590, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38156145

RESUMO

Cutaneous mixed tumour (CMT), also known as chondroid syringoma (CS), is a rare benign tumour composed of epithelial, myoepithelial, and mesenchymal components with an incidence of less than 0.01% of primary skin tumours. It is more common in males and typically presents as a painless slow-growing firm mass in the subcutis of the head and neck region. Genital regions are very rarely involved. We present the case of a 50-year-old male with a 10-year history of an asymptomatic gradually enlarging mass in the upper scrotum. A surgical excision was performed. Microscopic examination showed features of CMT. This case highlights the diagnostic challenges associated with scrotal CMT and surgical management of these lesions. Additionally, we endorse the recommended terminology of CMT used by the fifth edition of WHO Classification of Skin Tumours (2023).

2.
Br J Cancer ; 128(12): 2307-2317, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37085598

RESUMO

BACKGROUND: Soft tissue sarcomas (STS) are rare, heterogeneous tumours and biomarkers are needed to inform management. We previously derived a prognostic tumour microenvironment classifier (24-gene hypoxia signature). Here, we developed/validated an assay for clinical application. METHODS: Technical performance of targeted assays (Taqman low-density array, nanoString) was compared in 28 prospectively collected formalin-fixed, paraffin-embedded (FFPE) biopsies. The nanoString assay was biologically validated by comparing to HIF-1α/CAIX immunohistochemistry (IHC) in clinical samples. The Manchester (n = 165) and VORTEX Phase III trial (n = 203) cohorts were used for clinical validation. The primary outcome was overall survival (OS). RESULTS: Both assays demonstrated excellent reproducibility. The nanoString assay detected upregulation of the 24-gene signature under hypoxia in vitro, and 16/24 hypoxia genes were upregulated in tumours with high CAIX expression in vivo. Patients with hypoxia-high tumours had worse OS in the Manchester (HR 3.05, 95% CI 1.54-5.19, P = 0.0005) and VORTEX (HR 2.13, 95% CI 1.19-3.77, P = 0.009) cohorts. In the combined cohort, it was independently prognostic for OS (HR 2.24, 95% CI 1.42-3.53, P = 0.00096) and associated with worse local recurrence-free survival (HR 2.17, 95% CI 1.01-4.68, P = 0.04). CONCLUSIONS: This study comprehensively validates a microenvironment classifier befitting FFPE STS biopsies. Future uses include: (1) selecting high-risk patients for perioperative chemotherapy; and (2) biomarker-driven trials of hypoxia-targeted therapies.


Assuntos
Sarcoma , Hipóxia Tumoral , Humanos , Reprodutibilidade dos Testes , Prognóstico , Biomarcadores Tumorais/genética , Sarcoma/genética , Sarcoma/patologia , Hipóxia , Microambiente Tumoral
3.
Eur J Cancer ; 178: 216-226, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36470093

RESUMO

BACKGROUND: Adolescent and young adult (AYA) patients with cancer are poorly recruited to molecularly targeted trials and have not witnessed the advances in cancer treatment and survival seen in other age groups. We report here a pan-European proof-of-concept study to identify actionable alterations in some of the worst prognosis AYA cancers: bone and soft tissue sarcomas. DESIGN: Patients aged 12-29 years with newly diagnosed or recurrent, intermediate or high-grade bone and soft tissue sarcomas were recruited from six European countries. Pathological diagnoses were centrally reviewed. Formalin-fixed tissues were analysed by whole exome sequencing, methylation profiling and RNA sequencing and were discussed in a multidisciplinary, international molecular tumour board. RESULTS: Of 71 patients recruited, 48 (median 20 years, range 12-28) met eligibility criteria. Central pathological review confirmed, modified and re-classified the diagnosis in 41, 3, and 4 cases, respectively. Median turnaround time to discussion at molecular tumour board was 8.4 weeks. whole exome sequencing (n = 48), methylation profiling (n = 44, 85%) and RNA sequencing (n = 24, 50%) led to therapeutic recommendations for 81% patients, including 4 with germ line alterations. The most common were for agents targeted towards tyrosine kinases (n = 20 recommendations), DNA repair (n = 18) and the PI3K/mTOR/AKT pathway (n = 15). Recommendations were generally based on weak evidence such as activity in a different tumour type (n = 68, 61%), reflecting the dearth of relevant molecular clinical trial data in the same tumour type. CONCLUSIONS: We demonstrate here that comprehensive molecular profiling of AYA patients' samples is feasible and deliverable in a European programme.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Adolescente , Humanos , Adulto Jovem , Europa (Continente) , Sequenciamento do Exoma , Prognóstico , Sarcoma/genética , Sarcoma/terapia , Estudo de Prova de Conceito
4.
Clin Cancer Res ; 27(11): 3215-3223, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795258

RESUMO

PURPOSE: Cancer susceptibility and mortality are higher in males, and the mutational and transcriptomic landscape of cancer differs by sex. The current assumption is that men are at higher risk of epithelial cancers as they expose more to carcinogens and accumulate more damage than women. We present data showing women present with less aggressive primary cutaneous squamous cell carcinoma (cSCC) and early strong immune activation. EXPERIMENTAL DESIGN: We explored clinical and molecular sexual disparity in immunocompetent and immunosuppressed patients with primary cSCC (N = 738, N = 160), advanced-stage cSCC (N = 63, N = 20) and FVB/N mice exposed to equal doses of DMBA, as well as in human keratinocytes by whole-exome, bulk, and single-cell RNA sequencing. RESULTS: We show cSCC is more aggressive in men, and immunocompetent women develop mild cSCC, later in life. To test whether sex drives disparity, we exposed male and female mice to equal doses of carcinogen, and found males present with more aggressive, metastatic cSCC than females. Critically, females activate cancer immune-related expression pathways and CD4 and CD8 T-cell infiltration independently of mutations, a response that is absent in prednisolone-treated animals. In contrast, males increase the rate of mitosis and proliferation in response to carcinogen. Women's skin and keratinocytes also activate immune-cancer fighting pathways and immune cells at UV radiation-damaged sites. Critically, a compromised immune system leads to high-risk, aggressive cSCC specifically in women. CONCLUSIONS: This work shows the immune response is sex biased in cSCC and highlights female immunity offers greater protection than male immunity.


Assuntos
Carcinoma de Células Escamosas/imunologia , Suscetibilidade a Doenças/imunologia , Caracteres Sexuais , Neoplasias Cutâneas/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Carcinógenos/farmacologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/prevenção & controle , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos , Mitose/efeitos dos fármacos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/prevenção & controle
5.
BJR Open ; 3(1): 20200061, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35707756

RESUMO

Objective: Soft tissue sarcoma (STS) is a rare malignancy with a 5 year overall survival rate of 55%. Neoadjuvant radiotherapy is commonly used in preparation for surgery, but methods to assess early response are lacking despite pathological response at surgery being predictive of overall survival, local recurrence and distant metastasis. Multiparametric MR imaging (mpMRI) is used to assess response in a variety of tumours but lacks a robust, standardised method. The overall aim of this study was to develop a feasible imaging protocol to identify imaging biomarkers for further investigation. Methods: 15 patients with biopsy-confirmed STS suitable for pre-operative radiotherapy and radical surgery were imaged throughout treatment. The mpMRI protocol included anatomical, diffusion-weighted and dynamic contrast-enhanced imaging, giving estimates of apparent diffusion coefficient (ADC) and the area under the enhancement curve at 60 s (iAUC60). Histological analysis of resected tumours included detection of CD31, Ki67, hypoxia inducible factor and calculation of a hypoxia score. Results: There was a significant reduction in T1 at visit 2 and in ADC at visit 3. Significant associations were found between hypoxia and pre-treatment iAUC60, pre-treatment ADC and mid-treatment iAUC60. There was also statistically significant association between mid-treatment ADC and Ki67. Conclusion: This work showed that mpMRI throughout treatment is feasible in patients with STS having neoadjuvant radiotherapy. The relationships between imaging parameters, tissue biomarkers and clinical outcomes warrant further investigation. Advances in knowledge: mpMRI-based biomarkers have good correlation with STS tumour biology and are potentially of use for evaluation of radiotherapy response.

6.
Virchows Arch ; 478(5): 977-984, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32918169

RESUMO

Primary non-neuroendocrine tumours of the pituitary gland and sella are rare lesions often challenging to diagnose. We describe two cases of clinically aggressive primary glomus tumour of the pituitary gland. The lesions occurred in a 63-year-old male and a 30-year-old female who presented with headache, blurred vision and hypopituitarism. Neuroimaging demonstrated large sellar and suprasellar tumours invading the surrounding structures. Histologically, the lesions were characterised by angiocentric sheets and nests of atypical cells that expressed vimentin, smooth muscle actin and CD34. Perivascular deposition of collagen IV was also a feature. Case 2 expressed synaptophysin. INI-1 (SMARCB1) expression was preserved. Both lesions were mitotically active and demonstrated a Ki-67 labelling index of 30%. Next-generation sequencing performed in case 1 showed no mutations in the reading frame of 37 commonly mutated oncogenes, including BRAF and KRAS. Four pituitary glomus tumours have previously been reported, none of which showed features of malignant glomus tumour. Similar to our two patients, three previous examples displayed aggressive behaviour.


Assuntos
Tumor Glômico/patologia , Neoplasias Hipofisárias/patologia , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Diagnóstico Diferencial , Evolução Fatal , Feminino , Tumor Glômico/química , Tumor Glômico/diagnóstico por imagem , Tumor Glômico/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Hipofisárias/química , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/genética , Valor Preditivo dos Testes
7.
Int J Surg Pathol ; 29(3): 289-293, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32608312

RESUMO

E-cadherin is expressed in hematopoietic erythroid precursors, but to our knowledge, its expression in blastic plasmacytoid dendritic cell neoplasm (BPDCN) has not been described. We report a case of BPDCN showing strong expression of E-cadherin, arising in a patient with history of primary myelofibrosis. Four more cases of BPDCN tested all showed strong expression of E-cadherin. Lack of awareness of this pattern of expression may lead to erroneous diagnosis of acute erythroid leukemia. It is increasingly becoming important to correctly identify this group of neoplasms, as approved new anti-CD123-targeted therapies are becoming available.


Assuntos
Antígenos CD/análise , Medula Óssea/patologia , Caderinas/análise , Células Dendríticas/patologia , Neoplasias Hematológicas/diagnóstico , Mielofibrose Primária/patologia , Transformação Celular Neoplásica , Diagnóstico Diferencial , Evolução Fatal , Feminino , Neoplasias Hematológicas/patologia , Humanos , Leucemia Eritroblástica Aguda/diagnóstico , Leucemia Eritroblástica Aguda/patologia , Pessoa de Meia-Idade , Mielofibrose Primária/diagnóstico
8.
Urol Case Rep ; 35: 101537, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33364175

RESUMO

Renal myopericytoma is an extremely rare entity with just 11 cases reported in the literature. We report the case of a 57 year old Caucasian man who was found to have a renal myopericytoma following nephrectomy for suspected renal cell carcinoma. Renal myopericytoma has a distinct morphological overlap with other pericytic tumours and significant histological variation has been noted between cases reported to date. Further characterising this novel tumour is vital to identify subtypes within this spectrum, understand its behaviour and to identify imaging trends which may lead to pre-operative diagnosis in order to potentially avoid radical treatment.

9.
Int J Cancer ; 147(4): 1180-1184, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31465545

RESUMO

For most adolescent and young adult (AYA) cancers, age-specific molecular features are poorly understood. EORTC-SPECTA, an academic translational research infrastructure for biomaterial collection, will explicitly recruit AYA patients and will therefore collect empirical data to bridge the molecular gap between pediatric and adult oncology. The initial pilot study, activated in February 2019 across Europe, will recruit 100 AYA patients (aged 12-29 years) with newly diagnosed or relapsed high-grade gliomas and high-grade bone and soft tissue sarcomas. The primary objective of the pilot is to determine feasibility and recruitment rates. Formalin-fixed tumor tissue and whole blood from study participants will be prospectively collected with clinical data and stored centrally at the Integrated BioBank of Luxembourg. Whole exome sequencing of matched tumor and blood, and tumor RNA sequencing and DNA methylation profiling will be performed at the German Cancer Research Center, Heidelberg, Germany. Virtual central pathology review of scanned diagnostic slides will be undertaken by an international expert panel, and diagnostic material returned to the participating centers. A multidisciplinary molecular tumor board will release a clinically validated report to referring clinicians within 4-6 weeks after biopsy. SPECTA-AYA constitutes a major opportunity to gain knowledge about the tumor biology of this unique age group. It incorporates notable innovative aspects: AYA specificity, pan-European academic collaboration, centralized biobanking, comprehensive molecular profiling and virtual central pathology review, among others. SPECTA-AYA will help untangle the tumor particularities of AYAs with cancer and aims to improve their access to novel drugs and personalized medicine.


Assuntos
Bancos de Espécimes Biológicos/estatística & dados numéricos , Glioma/genética , Neoplasias/genética , Sarcoma/genética , Adolescente , Adulto , Metilação de DNA , Europa (Continente) , Feminino , Glioma/diagnóstico , Glioma/terapia , Humanos , Masculino , Oncologia/métodos , Oncologia/estatística & dados numéricos , Oncologia/tendências , Neoplasias/diagnóstico , Neoplasias/terapia , Projetos Piloto , Sarcoma/diagnóstico , Sarcoma/terapia , Análise de Sequência de RNA/métodos , Sequenciamento do Exoma/métodos , Adulto Jovem
10.
Fam Cancer ; 18(4): 445-449, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31240424

RESUMO

A 51-year old presented with a 6-month history of increasing pelvic/lower back pain with nocturnal waking and episodes of anorexia and vomiting. Examination revealed right torticollis and Horner's syndrome, and a large abdominal mass arising from the pelvis. Magnetic resonance and positron emission tomography imaging revealed (A) a 14 cm heterogeneous enhancing mass, abutting the left kidney with standardised uptake value max = 2.9, (B) a large heterogeneous enhancing pelvic mass (C) mesenteric adenopathy standardised uptake value max = 10.3 and (D) 6 cm right lung apex mass standardised uptake value max = 4.3. Computerised tomography-guided biopsy of lesion A was reported as neurofibroma with occasional atypia, lesion B a benign uterine leiomyoma and lesion C follicular lymphoma world health organisation Grade 2. Although she had been given the diagnosis of Neurofibromatosis Type-1 (NF1) 25-years previously following removal of an intradural extramedullary schwannoma she had no cutaneous stigmata of NF1. Genetic analysis of blood lymphocyte DNA identified a pathogenic variant in SMARCB1 confirming a diagnosis of schwannomatosis. Following 6-months chemotherapy for lymphoma, surgery was performed to remove lesion A. Histology revealed a malignant peripheral nerve sheath tumour with areas of low and high-grade change. An incidental, well-differentiated small bowel neuroendocrine carcinoma was also excised. Close surveillance continues with no recurrence after 6 years. This case study describes a novel finding of three separate synchronous primary malignancies in a patient with schwannomatosis and a proven SMARCB1 pathogenic variant.


Assuntos
Hemangioma/genética , Neoplasias Primárias Múltiplas/genética , Neurilemoma/genética , Neurofibromatoses/genética , Neurofibrossarcoma/genética , Proteína SMARCB1/genética , Neoplasias Cutâneas/genética , Feminino , Hemangioma/terapia , Síndrome de Horner/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/complicações , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Neurilemoma/complicações , Neurilemoma/patologia , Neurilemoma/terapia , Neurofibromatoses/complicações , Neurofibromatoses/terapia , Neurofibrossarcoma/patologia , Neurofibrossarcoma/terapia , Neoplasias Retroperitoneais/genética , Neoplasias Retroperitoneais/terapia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/terapia
11.
Leuk Lymphoma ; 59(7): 1586-1595, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29119842

RESUMO

We evaluated the outcomes for patients with peripheral T-cell lymphoma (PTCL) undergoing front-line chemotherapy at our institutions between 2002 and 2012. One hundred and fifty-six patients were eligible, comprising PTCL not otherwise specified (NOS) (n = 50, 32.0%), angioimmunoblastic T-cell lymphoma (AITL) (n = 44, 28.2%), anaplastic large-cell lymphoma (ALCL) ALK negative (n = 23, 14.7%), ALCL ALK positive (n = 16, 10.3%), and other (n = 23, 14.7%). Most patients received CHOP (66.0%) and 13.0% received an autologous hematopoietic progenitor cell transplant (HPCT). With a median follow-up of 63.4 months, 5-year overall survival (OS) and progression-free survival (PFS) was 38.8% and 19.8% respectively. Independent risk factors for inferior OS were age >60 years, International Prognostic Index (IPI) ≥ 2 and lack of complete response to induction. When responding patients were compared by receipt of an autologous HPCT versus not, HPCT was associated with improved PFS (p = .001) and OS (p = .046) and remained significant for PFS in multivariate analysis suggesting a possible therapeutic benefit.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Terapia Combinada , Quimioterapia de Consolidação , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Quimioterapia de Indução , Linfoma de Células T Periférico/diagnóstico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Recidiva , Análise de Sobrevida , Resultado do Tratamento , Reino Unido , Adulto Jovem
12.
Br J Cancer ; 118(5): 698-704, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29235571

RESUMO

BACKGROUND: Despite high metastasis rates, adjuvant/neoadjuvant systemic therapy for localised soft tissue sarcoma (STS) is not used routinely. Progress requires tailoring therapy to features of tumour biology, which need exploration in well-documented cohorts. Hypoxia has been linked to metastasis in STS and is targetable. This study evaluated hypoxia prognostic markers in the phase III adjuvant radiotherapy VorteX trial. METHODS: Formalin-fixed paraffin-embedded tumour biopsies, fresh tumour/normal tissue and blood were collected before radiotherapy. Immunohistochemistry for HIF-1α, CAIX and GLUT1 was performed on tissue microarrays and assessed by two scorers (one pathologist). Prognostic analysis of disease-free survival (DFS) used Kaplan-Meier and Cox regression. RESULTS: Biobank and outcome data were available for 203 out of 216 randomised patients. High CAIX expression was associated with worse DFS (hazard ratio 2.28, 95% confidence interval: 1.44-3.59, P<0.001). Hypoxia-inducible factor-1α and GLUT1 were not prognostic. Carbonic anhydrase IX remained prognostic in multivariable analysis. CONCLUSIONS: The VorteX-Biobank contains tissue with linked outcome data and is an important resource for research. This study confirms hypoxia is linked to poor prognosis in STS and suggests that CAIX may be the best known marker. However, overlap between single marker positivity was poor and future work will develop an STS hypoxia gene signature to account for tumour heterogeneity.


Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Anidrase Carbônica IX/metabolismo , Sarcoma/radioterapia , Regulação para Cima , Idoso , Bancos de Espécimes Biológicos , Hipóxia Celular , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Transportador de Glucose Tipo 1/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Radioterapia Adjuvante , Sarcoma/metabolismo , Sarcoma/cirurgia , Análise Serial de Tecidos , Pesquisa Translacional Biomédica , Reino Unido
15.
Cancer Chemother Pharmacol ; 74(2): 323-32, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24923562

RESUMO

PURPOSE: Our aims are to determine levels of circulating cellular and protein biomarkers in hepatocellular carcinoma (HCC) patients and to analyse any relationships with clinical parameters. METHODS: Fifty-four consenting patients were recruited. Circulating tumour cells (CTCs) were enumerated (by CellSearch) and characterised via filtration [by isolation by size of epithelial tumour cells (ISET)] with downstream immunohistochemistry (IHC). Glypican-3 (GPC3) expression in tumour biopsies and CTCs (by IHC) was compared, and levels of circulating caspase-cleaved and full-length cytokeratin 18 (CK18, measured using M30 and M65 ELISAs) were examined as a putative prognostic factor and marker of tumour burden. RESULTS: CTCs were identified in 14 out of 50 (28%) patients by CellSearch and in 19 out of 19 (100%) patients by ISET. The presence of GPC3-positive CTCs by ISET was 100% concordant with the presence of GPC3-positive cells in the original tumour (n = 5). No statistically significant correlations were observed between CTC number and clinical characteristics, although trends were noted between CTC subtypes, Child-Pugh score and tumour node metastasis stage. Serum M30 and M65 levels (as continuous variables) significantly correlated with overall survival (OS) in a univariate analysis (p = 0.003 and p < 0.001, respectively); M65 levels remained statistically significant in a multivariate analysis (p = 0.029). CONCLUSIONS: This is the first study to detect GPC3-positive CTCs in HCC, important for drug development with this target. The significant association of circulating CK18 with OS in HCC further exemplifies the utility of circulating biomarkers in cancer.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Separação Celular , Feminino , Seguimentos , Glipicanas/sangue , Humanos , Técnicas Imunoenzimáticas , Queratina-18/sangue , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
16.
Int J Surg Pathol ; 22(6): 512-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24788528

RESUMO

We describe 2 new cases of malignant melanoma with divergent rhabdomyoblastic differentiation occurring in adult patients. The patients were women aged 67 and 51 years with primary cutaneous and uterine cervical melanoma, respectively. Rhabdomyoblastic differentiation in melanoma is very rare in adult patients, and to our knowledge, only 7 such cases have been described in the world literature, of which only 4 have conclusive documentation of the presence of rhabdomyoblastic differentiation. We present the fifth and sixth cases of adult melanomas with conclusive divergent rhabdomyoblastic differentiation, including the first noncutaneous (cervical) case; we also review the literature and highlight the potential for underrecognition of this phenomenon.


Assuntos
Melanoma/patologia , Neoplasias Cutâneas/patologia , Neoplasias Uterinas/patologia , Idoso , Diferenciação Celular , Feminino , Humanos , Pessoa de Meia-Idade
18.
Int J Surg Pathol ; 22(5): 447-50, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24220998

RESUMO

Fibroblastic reticulum cells (FBRCs) belong to a major subtype of stromal support cells in the lymphoid system and rarely give rise to tumors. We report a case of fibroblastic reticulum cell tumor arising in the spleen. The tumor was clinically and radiologically mistaken for a metastatic deposit in the spleen. Microscopically the tumor was composed of spindle cells arranged in fascicles and storiform pattern. The cells had oval to elongated vesicular nuclei and pale eosinophilic cytoplasm with indistinct cell borders. There were admixed inflammatory cells, including large numbers of plasma cells. The tumor cells were positive for smooth muscle actin, desmin, AE1/AE3, and MNF116. They were negative for S100, CD1a, CD21, CD23, CD34, CD31, and CD35 among other markers. The morphological features and immunoprofile of this rare tumor in comparison to the few cases reported in the literature are discussed along with the positive reaction with cytokeratins and their relationship to the smaller subset of FBRCs, the cytokeratin-positive interstitial reticulum cells in the spleen.


Assuntos
Baço/patologia , Neoplasias Esplênicas/patologia , Células Estromais/patologia , Humanos , Queratinas/metabolismo , Masculino , Pessoa de Meia-Idade , Baço/metabolismo , Neoplasias Esplênicas/metabolismo , Células Estromais/metabolismo
19.
Melanoma Res ; 24(1): 40-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24201293

RESUMO

We previously demonstrated that circulating tumour cells (CTCs) are detectable by the MelCAM and high molecular weight melanoma-associated antigen (HMW-MAA)-dependent CellSearch platform. However, CTCs which do not express these capture and detection markers are not detectable by CellSearch. Consequently, we explored the use of isolation by size of epithelial tumour cells (ISET), a marker independent, filtration-based device to determine the prevalence and heterogeneity of CTCs in metastatic cutaneous melanoma patients. Ninety patients were prospectively recruited and blood samples taken before treatment. Patients' blood was filtered using the ISET platform. CTCs were enumerated using dual immunohistochemistry with positive selection by S100 expression and exclusion of leucocytes and endothelial cells expressing CD45 or CD144, respectively. A panel of markers (Melan-A, MITF, MelCAM, high molecular melanoma-associated antigen, CD271 and MAGEC) was also examined. Fifty-one patients (57%) had CTCs (range 1-44 CTCs/4 ml blood) and 12 patients also had circulating tumour microemboli. Seven patients had S100- CTCs, 11 patients' CTCs were S100+ and 33 patients had S100+ and S100- CTCs. Substantial intrapatient and interpatient heterogeneity was observed for all other melanoma-associated markers. CTCs in metastatic cutaneous melanoma are detectable using the flexible marker-independent ISET platform. CTCs display significant marker expression heterogeneity implying that marker-dependent platforms would not detect all CTCs and multimarker assays are now required to reveal the biological significance of this CTC heterogeneity.


Assuntos
Biomarcadores Tumorais/sangue , Melanoma/patologia , Células Neoplásicas Circulantes/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Heterogeneidade Genética , Humanos , Imunofenotipagem , Masculino , Melanoma/sangue , Melanoma/genética , Pessoa de Meia-Idade , Prevalência , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/genética , Melanoma Maligno Cutâneo
20.
Int J Surg Pathol ; 21(1): 29-36, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22843641

RESUMO

Some view ultrastructure as key to myofibrosarcoma diagnosis, whereas others argue that electron microscopy is too little used in contemporary practice to be considered an important diagnostic tool. These views are discussed in the context of 10 ultrastructurally confirmed cases of myofibrosarcoma, some occurring at rare sites such as skin and penis. Patient age ranged from 21 to 83 years, with a 6:4 male to female ratio. Size ranged from 2 to 7.5 cm and all had infiltrative margins. Histologically, all consisted of variably cellular fascicles of spindle cells with mild to moderately pleomorphic nuclei, small punctate nucleoli, and eosinophilic cytoplasm. All cases showed α-smooth muscle actin positivity and 2 showed very focal weak positivity for desmin. Ultrastructurally, the tumor cells contained rough endoplasmic reticulum, mainly peripheral smooth-muscle myofilaments, and fibronectin fibrils or fibronexus junctions at the cell surface. The most confident diagnosis of myofibrosarcoma is provided by ultrastructural examination. However, given the right histological appearance, use of a panel of antibodies that includes α-smooth muscle actin, desmin, and h-caldesmon, serves as an acceptable practical way of diagnosing myofibrosarcoma.


Assuntos
Fibrossarcoma/secundário , Miossarcoma/secundário , Neoplasias Cutâneas/patologia , Actinas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Tumor Desmoplásico de Pequenas Células Redondas/diagnóstico , Diagnóstico Diferencial , Retículo Endoplasmático Rugoso/ultraestrutura , Evolução Fatal , Feminino , Fibronectinas/ultraestrutura , Fibrossarcoma/metabolismo , Humanos , Imuno-Histoquímica/métodos , Masculino , Melanoma/diagnóstico , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Músculo Liso/ultraestrutura , Miofibrilas/ultraestrutura , Miossarcoma/metabolismo , Recidiva Local de Neoplasia , Pênis/patologia , Sarcoma/diagnóstico , Neoplasias Cutâneas/metabolismo , Xantomatose/diagnóstico , Adulto Jovem
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