Anaplastic large cell lymphoma with ALK::ATIC fusion mimicking a histiocytic sarcoma debuting as an anterior thoracic soft tissue tumor with exceptional clinicopathological, morphological and molecular features.

A 56-year-old woman debuted with a palpable painless mass in the anterior thorax wall at the level of the second and third right parasternal intercostal space, which progressively increased in size over 5 months accompanied by localized skin rash, mild dyspnea and chest pain when changing position. Imaging studies showed a soft tissue mass measuring 75 × 62 mm and a density of 34 Hounsfield Units that had caused the lysis of the costal arches and grew expansively towards the anterior mediastinum, without identifying mediastinal adenopathies only by this imaging method. Core biopsy was performed, which was initially diagnosed as histiocytic sarcoma (HS); however, when the diagnostic panel was expanded to include molecular and NGS studies, the final diagnosis was anaplastic large cell lymphoma with ALK::ATIC fusion. Here, we report a very rare neoplasm with unusual clinical presentation, histopathology and molecular features.

Carcinoma de células grandes de pulmón con inmunofenotipo nulo: reporte de caso y revisión breve de la literatura / Large cell carcinoma of the lung with null immunophenotype: Case report & brief review

El carcinoma de células grandes de pulmón con inmunofenotipo nulo (LCC-NI) constituye una entidad diagnóstica que hoy en día es especialmente infrecuente ya que no cuenta con ningún tipo de diferenciación celular o alteraciones moleculares propias. Representa un reto diagnóstico excepcional, el cual solo es posible realizar por exclusión contando con la resección quirúrgica, estudios de inmunohistoquímica y moleculares adecuados. Presentamos el caso de un varón de 69años de edad, con antecedente de alto índice tabáquico, que debuta con dolor pleurítico y tumor en el lóbulo pulmonar superior derecho, el cual se retira mediante lobectomía. A la evaluación patológica muestra una morfología de células grandes sin ningún inmunofenotipo, alteraciones moleculares o genómicas mediante estudios de secuenciación de siguiente generación (NGS), diagnosticándose como un LCC-NI.(AU)

Large cell carcinoma of the lung with null-immunophenotype (LCC-NI) is a diagnostic entity that is especially uncommon now as it does not have any type of cell differentiation or its own molecular alterations. It presents an exceptional diagnostic challenge; indeed, the diagnosis is only possible with complete surgical excision and adequate immunohistochemical and molecular studies. We report the case of a 69-year-old male, with a history of long-term smoking who presented with pleuritic pain. A tumor in the upper lobe of the right lung was detected and removed by lobectomy. Histopathology revealed a neoplasm with large cell morphology without any specific immunophenotype, molecular or genomic rearrangements through next-generation sequencing (NGS) studies, which was diagnosed as LCC-NI.(AU)

[Large cell carcinoma of the lung with null immunophenotype: Case report & brief review]. / Carcinoma de células grandes de pulmón con inmunofenotipo nulo: reporte de caso y revisión breve de la literatura.

Large cell carcinoma of the lung with null-immunophenotype (LCC-NI) is a diagnostic entity that is especially uncommon now as it does not have any type of cell differentiation or its own molecular alterations. It presents an exceptional diagnostic challenge; indeed, the diagnosis is only possible with complete surgical excision and adequate immunohistochemical and molecular studies. We report the case of a 69-year-old male, with a history of long-term smoking who presented with pleuritic pain. A tumor in the upper lobe of the right lung was detected and removed by lobectomy. Histopathology revealed a neoplasm with large cell morphology without any specific immunophenotype, molecular or genomic rearrangements through next-generation sequencing (NGS) studies, which was diagnosed as LCC-NI.

Aspergillus in liquid-based cervicovaginal cytology in a postmenopausal patient: A case report.

Aspergillus is an opportunistic fungus present in humid environments, whose natural environment is in soil, hay and compost. It is a frequent contaminant in the clinical laboratory. Because of this, the fungus is often inhaled, affecting those with an underlying pulmonary disease or immune deficiency. Fungal genitourinary tract infections are relatively common. A rare Aspergillus spp cervical infection diagnosed via liquid-based cytology is presented in the current study. The 57-year-old woman attended her annual check-up without any relevant medical history. The result of a gynecological examination by Papanicolaou smear was normal and routine liquid-based cytology was performed. The specimen exhibited fungal organisms characterized by septate hyphae branching at acute angles, most consistent with the Aspergillus species. Subsequent cytology demonstrated the same results. Antifungal treatment was initiated and a second post-treatment smear only exhibited atrophy. The cytomorphological features of Aspergillus spp. are discussed in the current study and a brief review of the few reported cases of a primary cervical infection in the literature is provided. In addition, the liquid-based cytology was established as a tool to diagnose the rare Aspergillus infection.

Systemic delivery and activation of the TRAIL gene in lungs, with magnetic nanoparticles of chitosan controlled by an external magnetic field.

Recently, functional therapies targeting a specific organ without affecting normal tissues have been designed. The use of magnetic force to reach this goal is studied in this work. Previously, we demonstrated that nanocarriers based on magnetic nanoparticles could be directed and retained in the lungs, with their gene expression under the control of a promoter activated by a magnetic field. Magnetic nanoparticles containing the TRAIL gene and chitosan were constructed using the ionic gelation method as a nanosystem for magnetofection and were characterized by microscopy, ζ-potential, and retention analysis. Magnetofection in the mouse melanoma cell line B16F10 in vitro induced TRAIL-protein expression and was associated with morphological changes indicative of apoptosis. Systemic administration of the nanosystem in the tail vein of mice with melanoma B16F10 at the lungs produced a very significant increase in apoptosis in tumoral cells that correlated with the number of melanoma tumor foci observed in the lungs. The high levels of apoptosis detected in the lungs were partially related to mouse survival. The data presented demonstrate that the magnetofection nanosystem described here efficiently induces apoptosis and growth inhibition of melanoma B16F10 in the lungs. This new approach for systemic delivery and activation of a gene based in a nanocomplex offers a potential application in magnetic gene delivery for cancer.

CXCL17 is a major chemotactic factor for lung macrophages.

Chemokines are a superfamily of chemotactic cytokines that direct the movement of cells throughout the body under homeostatic and inflammatory conditions. The mucosal chemokine CXCL17 was the last ligand of this superfamily to be characterized. Several recent studies have provided greater insight into the basic biology of this chemokine and have implicated CXCL17 in several human diseases. We sought to better characterize CXCL17's activity in vivo. To this end, we analyzed its chemoattractant properties in vivo and characterized a Cxcl17 (-/-) mouse. This mouse has a significantly reduced number of macrophages in its lungs compared with wild-type mice. In addition, we observed a concurrent increase in a new population of macrophage-like cells that are F4/80(+)CDllc(mid). These results indicate that CXCL17 is a novel macrophage chemoattractant that operates in mucosal tissues. Given the importance of macrophages in inflammation, these observations strongly suggest that CXCL17 is a major regulator of mucosal inflammatory responses.

TSPAN33 is a novel marker of activated and malignant B cells.

We have identified Tspan33 as a gene encoding a transmembrane protein exhibiting a restricted expression pattern including expression in activated B cells. TSPAN33 is a member of the tetraspanin family. TSPAN33 is not expressed in resting B cells, but is strongly induced in primary human B cells following activation. Human 2E2 cells, a Burkitt's lymphoma-derived B cell model of activation and differentiation, also upregulate TSPAN33 upon activation. TSPAN33 is expressed in several lymphomas including Hodgkin's and Diffuse large B cell lymphoma. TSPAN33 is also expressed in some autoimmune diseases where B cells participate in the pathology, including rheumatoid arthritis patients, systemic lupus erythematosus (SLE), and in spleen B cells from MRL/Fas(lpr/lpr) mice (a mouse model of SLE). We conclude that TSPAN33 may be used as a diagnostic biomarker or as a target for therapeutic antibodies for treatment of certain B cell lymphomas or autoimmune diseases.

CXCL17 is a mucosal chemokine elevated in idiopathic pulmonary fibrosis that exhibits broad antimicrobial activity.

The mucosal immune network is a crucial barrier preventing pathogens from entering the body. The network of immune cells that mediates the defensive mechanisms in the mucosa is likely shaped by chemokines, which attract a wide range of immune cells to specific sites of the body. Chemokines have been divided into homeostatic or inflammatory depending upon their expression patterns. Additionally, several chemokines mediate direct killing of invading pathogens, as exemplified by CCL28, a mucosa-associated chemokine that exhibits antimicrobial activity against a range of pathogens. CXCL17 was the last chemokine ligand to be described and is the 17th member of the CXC chemokine family. Its expression pattern in 105 human tissues and cells indicates that CXCL17 is a homeostatic, mucosa-associated chemokine. Its strategic expression in mucosal tissues suggests that it is involved in innate immunity and/or sterility of the mucosa. To test the latter hypothesis, we tested CXCL17 for possible antibacterial activity against a panel of pathogenic and opportunistic bacteria. Our results indicate that CXCL17 has potent antimicrobial activities and that its mechanism of antimicrobial action involves peptide-mediated bacterial membrane disruption. Because CXCL17 is strongly expressed in bronchi, we measured it in bronchoalveolar lavage fluids and observed that it is strongly upregulated in idiopathic pulmonary fibrosis. We conclude that CXCL17 is an antimicrobial mucosal chemokine that may play a role in the pathogenesis of interstitial lung diseases.

TLE1 is expressed in the majority of primary pleuropulmonary synovial sarcomas.

Pleuropulmonary synovial sarcoma (PPSS) is a rare entity, similar to synovial sarcoma of soft tissue (STSS). There are 120 published cases of PPSS, but no studies have explored the expression of TLE1. In soft tissues, it has been proven a useful marker, but in tumors of other sites, its expression has not been explored. The main objective was to study the expression and diagnostic sensitivity and specificity of TLE1 in a group of PPSS, of which the diagnosis was corroborated by fluorescence in situ hybridization confirming t(X;18) in a tissue microarray. Immunohistochemistry including TLE1, vimentin, CD99, CD56, bcl-2, AE1-AE3, EMA, CD34, CK7, CK19, calponin, and S-100 was performed on all PPSS and on 25 control cases (five carcinomas, ten mesotheliomas, and ten thoracic sarcomas). TLE1 was positive in 11 cases (73.3%); bcl-2 and vimentin in 100%; calponin and CD56 in 26.6%; CD99, CK AE1-AE3, CK19, CK7, and EMA in 80%; and S100 negative in all. The only biphasic PPSS was positive for epithelial markers only in the epithelial component. TLE1 was negative in all control cases. TLE1 is expressed in 73% of PPSS, a value inferior to that reported in STSS, but is highly specific for PPSS. TLE1 may therefore be of value in the differential diagnosis of PPSS, but should be used in a panel of antibodies.

[Her2-Neu expression in ductal adenocarcinomas of the breast gland: correlation with histopathological parameters and estrogen receptors' expression in Mexican patients]. / Expresión del Her2-Neu en el adenocarcinoma ductal de la glándula mamaria: correlación con parámetros histopatológicos y expresión de receptores estrogénicos en pacientes mexicanas.

BACKGROUND: Breast cancer is a general health problem that annually produces 400,000 deaths worldwide. Its early diagnosis leads to high cure rates; nevertheless, in Mexico City this happens rarely. Her2-Neu is an oncogene that is expressed on breast cancer cells, with aggressive behaviour and metastasis. In the United States 20 to 30% of the patients present an over-expression of this protein. This phenomenon has been used as a prognostic parameter and as a predictive and indication factor for therapy with monoclonal antibodies directed against this protein and for therapy with taxanes. OBJECTIVE: To know the biology and distribution of Her2-Neu expression in Mexican breast cancer patients in order to evaluate its potential as a prognostic and predictive factor in the treatment of the breast cancer. PATIENTS AND METHOD: In the cases of invasive ductal adenocarcinomas of the breast we compared by immunohistochemistry the Her2-Neu and estrogen receptor expressions with the histopathological characteristics. The results were evaluated statistically. RESULTS: We found 122 cases of breast adenocarcinoma, from which we evaluated 108 for fulfilling the selection criteria of invasive ductal adenocarcinoma. Patient's mean age was 51.8 +/- 13.2 years. The mean tumour diameter was 3.5 +/- 2.0 cm and the mean number of lymph nodes with metastasis was 6.8. The Her2-Neu (score 2+ and 3+) expression was found in 36.1% of the patients. The tumour diameter and the presence of metastatic disease had strong relation with the Her2-Neu expression level. We did not find correlation with the differentiation level, the patient's age and the presence or absence of oestrogen receptors. CONCLUSIONS: Since the percentage of patients with Her2-Neu expression is high (36.1%) and there is a close relation between Her2-Neu expression, the tumour size and the presence of lymph node methastasis, the determination of the oncoprotein expression could allow a more detailed prognosis and the treatment with immunotherapy and anthracyclines in order to influence the course of the breast cancer cases.