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1.
Histopathology ; 79(6): 1099-1107, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34431125

RESUMEN

BACKGROUND: Human herpesvirus-8 (HHV8) is a lymphotropic virus associated with different lymphoproliferative disorders, including primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD), diffuse large B-cell lymphomas, not otherwise specified, and the rare entity known as germinotropic lymphoproliferative disorder (GLPD). In PELs and GLPD the neoplastic cells also contain Epstein-Barr virus (EBV). In addition, occasional cases with atypical and overlapping features among these entities have been recognised, suggesting that the spectrum of the HHV8-related lesions may not be fully characterised. AIMS: Here, we report two cases of lymphoproliferative disorder associated with HHV8 and EBV that further expand the spectrum of HHV8/EBV-positive lymphoproliferative disease. METHODS AND RESULTS: Case 1 represented HHV8/EBV-positive extracavitary nodal PEL followed by pleural PEL. The striking characteristic of this case was the almost focal and intrasinusoidal localisation of the neoplastic cells and the association with Castleman's disease features. In the second case, we found the entire spectrum of HHV8-related disorders, i.e. MCD, GLPD, and PEL, coexisting in the same lymph node, underlining the variability, possible overlap and evolution among these entities. Both cases were well analysed with immunohistochemistry, determination of the EBV latency programme, and molecular analysis for clonality of immnoglobulin genes. In both patients, the disease followed an unexpected indolent course, both being still alive after 8 and 12 months, respectively. CONCLUSION: Our findings represent further evidence of the overlap among HHV8/EBV-positive lymphoproliferative disorders, and underline a grey zone that requires further study; they further confirm the experimental evidence that lytic EBV replication influences HHV8-related tumorigenesis.


Asunto(s)
Coinfección/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Herpesviridae/complicaciones , Trastornos Linfoproliferativos/virología , Activación Viral , Anciano , Evolución Clonal , Infecciones por Virus de Epstein-Barr/virología , Femenino , Infecciones por Herpesviridae/virología , Herpesvirus Humano 4/fisiología , Herpesvirus Humano 8 , Humanos , Trastornos Linfoproliferativos/patología , Masculino , Persona de Mediana Edad
2.
Am J Dermatopathol ; 43(5): 342-348, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33405402

RESUMEN

ABSTRACT: The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading throughout the world. The study describes 12 patients with SARS-CoV-2 pneumonia, who developed an acute erythematous rash with nonfollicular pinhead-sized pustules, without mucosal involvement. The clinical differential diagnosis was viral rash, acute generalized exanthematous pustulosis (AGEP), or multiform erythema. computed tomography with a diagnosis of interstitial pneumonia and a respiratory tract sample positive for SARS-CoV-2 in a reverse transcriptase polymerase chain reaction assay. Patients had signs of respiratory distress and were treated with hydroxychloroquine, darunavir, ritonavir, heparin, ceftriaxone, and azithromycin. Punch biopsies showed subcorneal pustules typical of AGEP. Dermal microvascular injury and thrombosis as described in skin damage by SARS-CoV-2 infection was not observed. The direct immunofluorescence for IgG, IgA, IgM, and C3 was negative in 8 patients investigated. A polymerase chain reaction for RNA SARS-CoV-2 performed on frozen skin was negative in 5 of 6 patients. Most of our patients were treated with systemic corticosteroids. After some days (4-10), the diffuse erythema and pustules had improved. AGEP is classified as a severe cutaneous adverse reaction, provoked by drugs and acute infections. Characteristically, removal of the offending agent leads to spontaneous resolution typically in less than 15 days. The recognition of AGEP is important, in order to avoid confusion with a systemic infection and consequently to avoid incorrect treatment. Cutaneous adverse reactions to drugs are common and are major health problems worldwide causing considerable costs for health care systems. We suggest that in the patients with AGEP during SARS-CoV-2 pneumonia, viral infection is a risk factor for developing drug reaction.


Asunto(s)
Pustulosis Exantematosa Generalizada Aguda/etiología , Antivirales/efectos adversos , Tratamiento Farmacológico de COVID-19 , Piel/efectos de los fármacos , Pustulosis Exantematosa Generalizada Aguda/tratamiento farmacológico , Pustulosis Exantematosa Generalizada Aguda/inmunología , Pustulosis Exantematosa Generalizada Aguda/virología , Corticoesteroides/uso terapéutico , Anciano , Anciano de 80 o más Años , Biopsia , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/virología , Prueba de Ácido Nucleico para COVID-19 , Diagnóstico Diferencial , Femenino , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/inmunología , Piel/inmunología , Piel/patología , Piel/virología , Resultado del Tratamiento
3.
Am J Dermatopathol ; 43(3): e38-e42, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-32769549

RESUMEN

ABSTRACT: Langerhans cell histiocytosis (LCH) is a clonal proliferation of bone-marrow-derived cells, which normally reside as epidermal and mucosal dendritic cells involved in antigen presentation. It is a rare disease more common in children than adults, that is believed to be neoplastic in most cases. The diagnosis is based on clinical and radiological findings in combination with histopathologic, immunophenotypic, or ultrastructural analyses. LCH have a broad spectrum of clinical manifestations, ranging from benign cutaneous lesions to malignant multisystem disease. Based on the extent of involvement at diagnosis, LCH can be divided in single-system LCH when only one organ or system is involved, usually with multiple lesions, and multisystem LCH, when 2 or more organs or systems are involved at diagnosis. One variant of LCH is characterized by congenital isolated cutaneous involvement. It typically manifests at birth or in the postnatal period with a widespread eruption of red-to-brown papulo-nodules or, more uncommonly, a solitary lesion. The overall prognosis for single lesion skin limited LCH is excellent and most lesions spontaneously resolve within 4-18 weeks. Systemic involvement is rare. Skin findings cannot predict systemic disease and obtaining an oncology consultation is recommended for further evaluation. Herein, we present an additional case in a full-term, well-appearing, female infant with an isolated, asymptomatic, ulcerated, papule of the left arm, that was noted at birth.


Asunto(s)
Histiocitosis de Células de Langerhans/patología , Enfermedades de la Piel/patología , Femenino , Histiocitosis de Células de Langerhans/congénito , Humanos , Recién Nacido , Remisión Espontánea , Enfermedades de la Piel/congénito
4.
Pathologica ; 113(6): 449-455, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34974551

RESUMEN

Trichogerminoma, first described by Sau et al. in 1992, is a rare cutaneous adnexal neoplasm of the hair germ cell and usually associated with benign clinical course and favorable outcome. About 30 cases have been reported, all with similar histological features. However, due to a small but potential risk of malignancy, complete excision of the tumor is the treatment of choice. There is still controversy over its inclusion into the spectrum of trichoblastoma.Herein, we report an additional case occurring in the left buttock of a 47-year-old female, presenting with a subcutaneous solitary nodule composed of lobules of basaloid cells, with peripheral palisading and round cell nests or "cell balls" arranged in the central part. The lobules are separated by a fibrous or myxoid stroma. There are no clefts separating the tumor cells and surrounding stroma, but clefts separating stroma by the surrounding adipose tissue can be seen. Typical mitotic figures are frequently present (4-5 per 10 high-power fields). Immunohistochemistry shows the tumor cells are positive for pan-CK (AE1/AE3), CK5/6, p40, GATA 3, whereas they are negative for CK7, CK20, chromogranin A, synaptofisin, androgen receptor, estrogen receptor, and calretinin. Staining for CK20, synaptofisin, and chromogranin A detect Merkel cells scattered within the lobules. Ki67 highlights a nuclear proliferative rate of about 20%.Trichogerminoma should be distinguished from other trichogenic tumors made up of basoloid cells or hair follicular differentiation. The mainly differential diagnosis includes trichoblastoma, trichoepitelioma, tricholemmoma, and basal cell carcinoma.Herein, we report a case of trichogerminoma which, unlike the cases previously reported, showed numerous mitotic figures and a higher Ki67 nuclear proliferative rate.


Asunto(s)
Enfermedades del Cabello , Neoplasias Cutáneas , Biomarcadores de Tumor , Femenino , Folículo Piloso , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Piel
5.
Pathologica ; 113(6): 421-426, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34974547

RESUMEN

AIM: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma, with an increasing worldwide incidence. It presents as a painless red to purple nodule on sun-exposed skin. MCC is presumed to arise from resident cutaneous Merkel cells. The pathogenesis of MCC is likely multifactorial with immunosuppression, UV-induced skin damage, and Merkel cell polyomavirus contributing to the development. The diagnosis of MCC relies upon characteristic morphologic features and use of immunohistochemical stains. Histologically, the differential diagnosis of Merkel cell carcinoma includes the 'small round cell' tumor group, particularly metastatic small cell carcinoma and hematological malignancies. This study investigates the expression of NeuN antibody, which recognizes the protein NeuN, normally present in most neuronal cell types and neuronal tumors, in Merkel cell carcinomas. METHODS AND RESULTS: Fifteen cases of Merkel cell carcinoma (7 men and 7 women; mean age 74 years) were retrieved from the institute database between the years 2011-2020. The immunohistochemical profile was investigated: CK20 (14/14), Neurofilament, (12/12), Synaptophysin (14/14); Chromogranin A (11/13), PAX5 (10/12), TDT (5/12), CK7 (1/14), TTF1 (0/14). Infection by Polyoma virus was detected in 11 of 14 patients. Most tumors showed middle/strong expression of NeuN. No cutaneous structures, or epidermal Merkel cells, showed expression of NeuN. The expression of NeuN was investigated in 17 primary small cell lung carcinomas: 2 cases were positive for Neu-N. CONCLUSIONS: Awareness of the staining pattern of Neu-N could aid in diagnosis of Merkel cell carcinoma, avoiding misinterpretation and erroneous diagnosis with other tumors.


Asunto(s)
Carcinoma de Células de Merkel , Neoplasias Cutáneas , Anciano , Carcinoma de Células de Merkel/diagnóstico , Proteínas Portadoras , ADN , Femenino , Humanos , Masculino , Neuronas , Neoplasias Cutáneas/diagnóstico
6.
Pathologica ; 113(4): 285-293, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34463673

RESUMEN

Multiple myeloma accounts for 10-15% of all hematologic malignancies, and 20% of deaths related to cancers of the blood and bone marrow. Diagnosis is defined by the presence of a serum monoclonal spike (M-spike) of more than 3 g/dL or more than 10% clonal plasma cells in the bone marrow and at least one myeloma-defining event, such as hypercalcemia, anemia, bone lesions, or renal impairment. The kidney is a major target organ, and renal impairment is frequently the first manifestation of the disease. Renal damage occurs in up to 40% of patients and 10-20% will require dialysis. Monoclonal immunoglobulin light chains are the major causes of renal complications in multiple myeloma. Glomerular disease, with the deposition of monoclonal immunoglobulins or their components, includes monoclonal immunoglobulin deposition disease, AL or AH amyloidosis, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits, immunotactoid glomerulopathy, and fibrillary glomerulonephritis. In addition, tubulointerstitial diseases with the deposition of monoclonal immunoglobulins or their components, are constituted by light chain cast nephropathy, light chain proximal tubulopathy, and crystal-storing histiocytosis.We report the case of a 66-year-old woman who presented with albumin-predominant moderate proteinuria and renal failure. Serum and urine immunofixation electrophoresis showed monoclonal κ light chain in both. Renal biopsy confirmed κ-restricted crystal-storing renal disease involving proximal tubular epithelial cells and crystal storing histiocytosis. Multiple myeloma with crystal storing histiocytosis was discovered in bone marrow biopsy. Thus, we present an unusual case of a myeloma patient presenting light chain proximal tubulopathy and crystal-storing histiocytosis both in the kidney and in the bone marrow.


Asunto(s)
Histiocitosis , Enfermedades Renales , Mieloma Múltiple , Paraproteinemias , Anciano , Femenino , Histiocitosis/complicaciones , Humanos , Riñón , Mieloma Múltiple/complicaciones , Paraproteinemias/complicaciones
7.
Clin Gastroenterol Hepatol ; 18(10): 2375-2377, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32480008

RESUMEN

Coronavirus disease 2019 (COVID-19) is a major worldwide threat caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly spreading to a global pandemic. As of May 11, 2020, 4,176,346 cases have been reported worldwide, 219,814 in Italy, and of them, 81,871 occurred in the Lombardy region.1 Although the respiratory manifestations of COVID-19 have been widely described, the impact on the gastrointestinal (GI) system remains less clear. The reported prevalence of digestive symptoms ranges from 3% to 79%, depending on the setting,2-5 but data on GI endoscopic and histologic findings in COVID-19 patients are lacking. Therefore, the aim of this study is to describe the GI endoscopic and histologic findings in COVID-19 patients.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/diagnóstico , Enfermedades del Sistema Digestivo/diagnóstico , Endoscopía Gastrointestinal/métodos , Neumonía Viral/diagnóstico , Anciano , COVID-19 , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Enfermedades del Sistema Digestivo/etiología , Femenino , Humanos , Italia/epidemiología , Masculino , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Estudios Retrospectivos , SARS-CoV-2
8.
Pathologica ; 112(1): 50-55, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32202540

RESUMEN

We describe an 18-year-old woman with several month's history of a 12 x 7 mm palpable mammary nodule, that was hypoechoic, with regular margins and vascularization areas by ultrasound. A fibroadenoma was hypothesized (American College of Radiology BI-RADS 3). A 14 G needle biopsy was performed, showing a LC proliferation suspected for LCH of a lymph node, with florid dermatopathic lymphadenopathy in differential diagnosis. The multidisciplinary team of the breast clinic decided to perform a lumpectomy and a diagnosis of LCH involving an intra-mammary lymph node was made. Langerhans cells (LC) are dendritic cells characterized by grooved nuclei, irregular nuclear contours, and abundant cytoplasm, that normally reside in the skin and mucosal surfaces. They were positive for CD1a, langerin/CD207, and S100 by immunohistochemistry. Langerhans cell histiocytosis (LCH) is a clonal proliferation of histiocytes that is thought to be neoplastic in most cases. Reactive LC can be distinguished from LCH by cyclin D1 immunostaining, which is positive only in LCH. About 50% of cases have BRAF V600E mutations. The revised classification of histiocytes divides LCH in subtypes: LCH SS (single system), LCH lung positive, LCH Multiple System/Risk Organ negative and LCH Multiple System/Risk Organ positive. Localized disease can progress to multisystem involvement. The diagnosis of LCH is based on clinical and radiological findings in combination with histopathological, immunophenotypic or ultrastructural analyses identifying tissue infiltration by LC. It is recommended that biopsy confirmation of suspected LCH be performed in all cases. Lymph nodes may be the only site of disease or a part of multisystem involvement by LCH. The histologic differential diagnosis is discussed.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Histiocitosis de Células de Langerhans/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Glándulas Mamarias Humanas/diagnóstico por imagen , Adolescente , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/cirugía , Femenino , Histiocitosis de Células de Langerhans/complicaciones , Histiocitosis de Células de Langerhans/cirugía , Humanos , Ganglios Linfáticos/cirugía , Glándulas Mamarias Humanas/cirugía
9.
Tumour Biol ; 39(4): 1010428317695023, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28378631

RESUMEN

The importance of the immune system as a potent anti-tumor defense has been consolidated in recent times, and novel immune-related therapies are today demonstrating a strong clinical benefit in the setting of several solid neoplasms. Tumor-infiltrating lymphocytes reflect the attempt of the host to eradicate malignancies, and during the last decades, they have been shown to possess an interesting prognostic utility for breast cancer, especially in case of HER2 positive and triple-negative molecular subtypes. In parallel, the clinical evaluation of tumor-infiltrating lymphocytes has been shown to effectively predict treatment outcomes in both neoadjuvant and adjuvant settings. Currently, tumor-infiltrating lymphocytes are promising further predictive utility in view of novel immune-related therapeutic strategies which are coming into the clinical setting launching a solid rationale for the future next-generation treatment options. In this scenario, tumor-infiltrating lymphocytes might represent an important resource for the selection of the most appropriate therapeutic strategy, as well as further evaluations of the molecular mechanisms underlying tumor-infiltrating lymphocytes and the immunoediting process would eventually provide new insights to augment therapeutic success. Considering these perspectives, we review the potential utility of tumor-infiltrating lymphocytes in the definition of breast cancer prognosis and in the prediction of treatment outcomes, along with the new promising molecular-based therapeutic discoveries.


Asunto(s)
Neoplasias de la Mama/terapia , Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/inmunología , Femenino , Humanos , Terapia Neoadyuvante , Pronóstico , Resultado del Tratamiento
12.
World Neurosurg ; 182: 83-90, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37995988

RESUMEN

OBJECTIVE: Intracranial dermoid cyst (DC) is a rare benign, slow-growing lesion, most commonly arising along the midline. They can occur in the supratentorial compartment, very rarely involve the sellar region and only exceptionally are intrasellar. The aim of our study is to address the challenges in the diagnosis and management of sellar DCs. METHODS: We performed a systematic review of sellar DCs, in keeping with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and described an intrasellar DC in a 32-year-old female who presented with bilateral blurring vision. RESULTS: The review identified 4 intrasellar, 29 suprasellar, and 28 parasellar cases. Intrasellar DCs more likely present with progressive visual impairment and pituitary hormone dysfunctions during the fifth decade of life. Suprasellar and parasellar DCs are typically diagnosed during the third decade of life because of diplopia, ptosis, trigeminal hypoaesthesia/para-esthesia or cyst's rupture. Sellar DCs are typically hypodense on computed tomography scans and contain calcifications. Magnetic resonance imaging features include T1 hyperintensity, T2 heterogeneous intensity, no restriction on diffusion-weighted images, and no contrast enhancement. Surgery is the treatment of choice. Gross total resection is achieved in 60% of intrasellar and 61.9% of suprasellar and parasellar DCs. Early postoperative complications are reported in 40.0%, 16.7%, and 23.8% of intrasellar, suprasellar, and parasellar DCs, respectively. CONCLUSIONS: Intrasellar DCs are rare lesions typically diagnosed later than suprasellar and parasellar DCs due to their different clinical presentations. However, they should be considered in the differential diagnosis of cystic lesions of the sella, including epidermoid cysts, craniopharyngiomas, Rathke's cleft cysts, and teratomas.


Asunto(s)
Quistes del Sistema Nervioso Central , Quiste Dermoide , Quiste Epidérmico , Neoplasias Hipofisarias , Femenino , Humanos , Adulto , Quiste Dermoide/diagnóstico por imagen , Quiste Dermoide/cirugía , Quiste Dermoide/complicaciones , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Quistes del Sistema Nervioso Central/cirugía , Quistes del Sistema Nervioso Central/complicaciones , Quiste Epidérmico/complicaciones , Imagen por Resonancia Magnética , Silla Turca/diagnóstico por imagen , Silla Turca/cirugía , Silla Turca/patología
13.
Cells ; 13(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38607036

RESUMEN

Glioblastoma is the most frequent and aggressive brain tumor in adults. This study aims to evaluate the expression and prognostic impact of CD99, a membrane glycoprotein involved in cellular migration and invasion. In a cohort of patients with glioblastoma treated with surgery, radiotherapy and temozolomide, we retrospectively analyzed tumor expression of CD99 by immunohistochemistry (IHC) and by quantitative real-time polymerase chain reaction (qRT-PCR) for both the wild type (CD99wt) and the truncated (CD99sh) isoforms. The impact on overall survival (OS) was assessed with the Kaplan-Meier method and log-rank test and by multivariable Cox regression. Forty-six patients with glioblastoma entered this study. Immunohistochemical expression of CD99 was present in 83%. Only the CD99wt isoform was detected by qRT-PCR and was significantly correlated with CD99 expression evaluated by IHC (rho = 0.309, p = 0.037). CD99 expression was not associated with OS, regardless of the assessment methodology used (p = 0.61 for qRT-PCR and p = 0.73 for IHC). In an exploratory analysis of The Cancer Genome Atlas, casuistry of glioblastomas CD99 expression was not associated with OS nor with progression-free survival. This study confirms a high expression of CD99 in glioblastoma but does not show any significant impact on survival. Further preclinical studies are needed to define its role as a therapeutic target in glioblastoma.


Asunto(s)
Glioblastoma , Adulto , Humanos , Glioblastoma/tratamiento farmacológico , Estudios de Cohortes , Pronóstico , Estudios Retrospectivos , Temozolomida/uso terapéutico , Antígeno 12E7
14.
Biomedicines ; 11(2)2023 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-36830847

RESUMEN

With the advent of immunotherapies, the field of cancer therapy has been revived with new hope, especially for cancers with dismal prognoses, such as the glioblastoma multiforme (GBM). Currently, immunotherapies should potentiate the host's own antitumor immune response against cancer cells, but it has been documented that they are effective only in small subsets of patients. Therefore, accurate predictors of response are urgently needed to identify who will benefit from immune-modulatory therapies. Brain tumors are challenging in terms of treatments. The immune response in the brain is highly regulated, and the immune microenvironment in brain metastases is active with a high density of tumor-infiltrating lymphocytes (TILs, CD3+ T cells) in certain patients and, therefore, may serve as a potential treatment target. In our study, we performed immunohistochemistry for CD3 and PD-L1 along the routine assessment of the O6-methylguanine-methyltransferase (MGMT) promoter methylation status and the IDH1 and 2 status in a single center cohort of 69 patients with GBM (58 primary tumors and 11 recurrences) who underwent standard multimodal therapies (surgery/radiotherapy/adjuvant temozolamide). We analyzed the association of PD-L1 tumor expression and TILs with overall survival (OS). The PD-L1 expression was observed in 25 of 58 (43%) newly diagnosed primary glioblastoma specimens. The sparse-to-moderate density of TILs, identified with CD3+ expression, was found in 48 of 58 (83%) specimens. Neither PD-L1 expression nor TILs were associated with overall survival. In conclusion, TILs and/or PD-L1 expression are detectable in the majority of glioblastoma samples, and even if they slightly relate to the outcome, they do not show a statistically significant correlation.

15.
Sci Rep ; 13(1): 11951, 2023 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-37488154

RESUMEN

Mathematical models based on partial differential equations (PDEs) can be exploited to handle clinical data with space/time dimensions, e.g. tumor growth challenged by neoadjuvant therapy. A model based on simplified assessment of tumor malignancy and pharmacodynamics efficiency was exercised to discover new metrics of patient prognosis in the OLTRE trial. We tested in a 17-patients cohort affected by early-stage triple negative breast cancer (TNBC) treated with 3 weeks of olaparib, the capability of a PDEs-based reactive-diffusive model of tumor growth to efficiently predict the response to olaparib in terms of SUVmax detected at 18FDG-PET/CT scan, by using specific terms to characterize tumor diffusion and proliferation. Computations were performed with COMSOL Multiphysics. Driving parameters governing the mathematical model were selected with Pearson's correlations. Discrepancies between actual and computed SUVmax values were assessed with Student's t test and Wilcoxon rank sum test. The correlation between post-olaparib true and computed SUVmax was assessed with Pearson's r and Spearman's rho. After defining the proper mathematical assumptions, the nominal drug efficiency (εPD) and tumor malignancy (rc) were computationally evaluated. The former parameter reflected the activity of olaparib on the tumor, while the latter represented the growth rate of metabolic activity as detected by SUVmax. εPD was found to be directly dependent on basal tumor-infiltrating lymphocytes (TILs) and Ki67% and was detectable through proper linear regression functions according to TILs values, while rc was represented by the baseline Ki67-to-TILs ratio. Predicted post-olaparib SUV*max did not significantly differ from original post-olaparib SUVmax in the overall, gBRCA-mutant and gBRCA-wild-type subpopulations (p > 0.05 in all cases), showing strong positive correlation (r = 0.9 and rho = 0.9, p < 0.0001 both). A model of simplified tumor dynamics was exercised to effectively produce an upfront prediction of efficacy of 3-week neoadjuvant olaparib in terms of SUVmax. Prospective evaluation in independent cohorts and correlation of these outcomes with more recognized efficacy endpoints is now warranted for model confirmation and tailoring of escalated/de-escalated therapeutic strategies for early-TNBC patients.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Antígeno Ki-67 , Tomografía Computarizada por Tomografía de Emisión de Positrones
16.
Histopathology ; 61(4): 629-43, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22882517

RESUMEN

AIMS: The aim of this study was to devise a molecular classification for salivary duct carcinomas (SDCs) based on the similarities between SDCs and breast carcinomas and on characteristics of the microarray-based gene expression profiling-defined molecular subtypes of breast cancer. METHODS AND RESULTS: Forty-two pure salivary duct carcinomas, 35 of which contained an in-situ component as defined by histological review and/or immunohistochemical analysis, were stained with antibodies for oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5/6. Based on these markers, tumours were classified into HER2, luminal androgen receptor-positive, basal-like, luminal and indeterminate phenotype. Analysis revealed that 16.7%, 69%, 4.8%, 9.5% and 0% were of HER2, luminal androgen receptor-positive, basal-like, indeterminate and luminal phenotype, respectively. The in-situ and invasive components displayed the same molecular subtype in all but one case. CONCLUSION: Salivary duct carcinomas can be classified into molecular subgroups approximately equivalent to those in the breast. We also report on the existence of a subgroup of bona fide pure salivary duct carcinomas that have a 'basal-like' phenotype. Understanding the phenotypic complexity of SDCs may help to expedite the identification of novel therapeutic targets for these aggressive tumours.


Asunto(s)
Carcinoma in Situ/clasificación , Carcinoma Ductal/clasificación , Carcinoma/clasificación , Neoplasias de las Glándulas Salivales/clasificación , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Carcinoma/genética , Carcinoma/patología , Carcinoma in Situ/genética , Carcinoma in Situ/patología , Carcinoma Ductal/genética , Carcinoma Ductal/patología , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Receptor ErbB-2/análisis , Receptor ErbB-2/biosíntesis , Receptor ErbB-2/genética , Receptores Androgénicos/análisis , Receptores Androgénicos/biosíntesis , Receptores Androgénicos/genética , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/patología , Análisis de Matrices Tisulares , Transcriptoma
17.
Exp Dermatol ; 21(2): 86-90, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22103332

RESUMEN

Previous studies have reported that repeated solar and artificial UVB (280-320 nm) and UVA (320-400 nm) exposures can modify acquired melanocytic nevi (AMN). We therefore investigated the clinical, dermoscopic, histological and immunohistochemical changes in AMN exposed to UVB and UVA radiation. Twenty healthy volunteers with at least three AMN on the trunk were enrolled in the present study and randomized into two groups to receive equally effective doses of narrow-band (NB)-UVB or UVA1. Three exposures per week were delivered for a total of 4 weeks. During exposures, one AMN was left unprotected, a second one was shielded with an opaque adhesive tape and the third nevus was covered with a commercial sunscreen. After the irradiation cycle, the AMN were surgically removed and underwent histological and immunohistochemical assessment of melanocyte/melanogenesis-related proteins (MART-1, tyrosinase, HMB-45), cell cycle activation markers (Ki-67, topoisomerase IIalpha, p53, Cdk2) and transcription factors (microphthalmia-associated transcription factor, STAT3). Nevi that were exposed to NB-UVB or UVA1 also showed statistically significant increase in size and changes in their dermoscopic features, including overall darkening, increased pigment network expression, formation of branched streaks, and increased number and size of brown globules and dots. AMN that had been covered with opaque tape or sunscreen did not show changes in size or dermoscopic features following UVA1 or NB-UVB exposure. Histological and immunohistochemical analysis did not show any significant change in exposed AMN in comparison with AMN shielded with an opaque adhesive tape or covered with the sunscreen.


Asunto(s)
Nevo Pigmentado/metabolismo , Nevo Pigmentado/patología , Piel/efectos de la radiación , Rayos Ultravioleta , Adulto , Anciano , Antígenos de Neoplasias/metabolismo , Quinasa 2 Dependiente de la Ciclina/metabolismo , ADN-Topoisomerasas de Tipo II/metabolismo , Proteínas de Unión al ADN/metabolismo , Dermoscopía , Femenino , Técnicas Histológicas , Humanos , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Antígeno MART-1/metabolismo , Masculino , Antígenos Específicos del Melanoma/metabolismo , Factor de Transcripción Asociado a Microftalmía/metabolismo , Persona de Mediana Edad , Monofenol Monooxigenasa/metabolismo , Factor de Transcripción STAT3/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Antígeno gp100 del Melanoma
18.
G Ital Nefrol ; 39(3)2022 Jun 20.
Artículo en Italiano | MEDLINE | ID: mdl-35819044

RESUMEN

Staphylococcus-associated glomerulonephritis (SAGN) represents a possible version of parainfectious glomerulonephritis and is a pathological entity that's now constantly increasing in developed countries. It is known how bacterial infections can be a possible trigger for various type of glomerulonephritis with clinical onset and evolution comparable to the ones observed in parainfectious glomerulonephritis. Furthermore, in clinical practice the identification and isolation of the pathogenic microorganism responsible for the development of parainfectious glomerulonephritis is not always possible. Therefore, in those cases in which SAGN is suspected, it is often necessary to recur to kidney biopsy in order to come to as much as possible correct diagnosis. Historically, according to scientific literature, the most distinctive anatomopathological feature of SAGN is represented by predominant or codominant mesangial IgA deposits, sometimes associated with C3 deposits. These findings make the differential diagnosis between SAGN and IgA nephropathy often necessary. However, many reports describe how SAGN can also be characterized by a varying spectrum of immunological deposits. In some cases, for example, IgA deposits can be absent and in some other cases it is described a net dominance of C3 deposits. In this case, it becomes extremely important to exclude a possible occurrence of C3 glomerulopathy (C3GN), considering how different are the therapeutic approach and the prognostic implications associated to it. However, the differential diagnosis between SAGN and C3GN can be very hard. Here's a case report about a patient who has been hospitalized into our Unit after developing a form of Staphylococcus Aureus associated glomerulonephritis which presented atypical anatomopathological features.


Asunto(s)
Glomerulonefritis por IGA , Glomerulonefritis , Infecciones Estafilocócicas , Glomerulonefritis/complicaciones , Glomerulonefritis/diagnóstico , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/diagnóstico , Humanos , Inmunoglobulina A , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/diagnóstico , Staphylococcus
19.
Clin J Gastroenterol ; 15(6): 1072-1077, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36100806

RESUMEN

Gastrointestinal tract is an uncommon site of breast cancer metastasis. Rectal linitis plastica (RLP) is a rare presentation of rectal neoplasia, both primary and secondary, and refers to a diffuse infiltration of the wall by an infiltrating carcinoma. Diagnostic assessment of RLP may be challenging since cross-sectional imaging and endoscopic findings may be nonspecific, and endoscopic biopsies are frequently non-diagnostic due to the submucosal disease localization. Endoscopic ultrasound (EUS) with fine needle biopsy (FNB) is widely used for the diagnostic assessment of sub-epithelial lesions of upper and lower gastrointestinal tract. However, data about the use of EUS in case of rectal linitis plastica are very poor. We present a case of rectal metastasis as the first presentation of lobular breast cancer, presenting as rectal linitis plastica and diagnosed with EUS-FNB.


Asunto(s)
Neoplasias de la Mama , Carcinoma Lobular , Linitis Plástica , Neoplasias del Recto , Neoplasias Gástricas , Humanos , Femenino , Linitis Plástica/diagnóstico por imagen , Linitis Plástica/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Carcinoma Lobular/diagnóstico por imagen , Carcinoma Lobular/secundario , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/patología , Biopsia con Aguja Fina , Neoplasias Gástricas/patología
20.
Pediatr Dermatol ; 28(5): 555-60, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21062348

RESUMEN

The lines of Blaschko are a cutaneous pattern of mosaicism present in a variety of skin disorders. Developmental abnormalities affecting other tissues derived from the embryonic ectoderm and mesoderm are sometimes associated. Here, we describe a 5-year-old boy with basaloid follicular hamartoma affecting the left side of the body in linear multiple bands, following Blaschko lines. Lesions were predominantly hypopigmented macules and streaks, but among these, we could observe brownish atrophic patches and brown papules. Furthermore, ipsilateral hemimegaloencephaly and microphthalmia were present. These findings suggest a neurocutaneous condition recently described by Happle and Tinschert. Its nosologic classification will be discussed.


Asunto(s)
Hamartoma/diagnóstico , Malformaciones del Desarrollo Cortical/diagnóstico , Microftalmía/diagnóstico , Neoplasias Cutáneas/diagnóstico , Preescolar , Hamartoma/congénito , Hamartoma/patología , Humanos , Masculino , Malformaciones del Desarrollo Cortical/genética , Malformaciones del Desarrollo Cortical/patología , Microftalmía/genética , Microftalmía/patología , Mosaicismo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología
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