RESUMO
BACKGROUND: Granulomatosis with polyangiitis (GPA) is characterized by necrotizing granulomatous inflammation with necrotizing vasculitis predominantly affecting small to medium vessels. The survival rates have drastically improved; however, GPA can be lethal, with older patients having a worse prognosis and higher mortality than younger patients. Moreover, the incidence of various cancers has been reported to increase in patients with GPA. We aimed to discuss possible associations between GPA and lung cancer and emphasize the associated diagnostic challenges. CASE PRESENTATION: We encountered three older patients with chronic GPA who developed lung cancer during long-term follow-up. Two of the patients had a smoking history, with one having silicosis and the other having chronic obstructive pulmonary disease. Furthermore, all of them had radiation exposure from repeated radiography/computed tomography. All the patients had confirmed GPA, and vasculitis relapse was first suspected when new lung lesions were noted during follow-up. However, they had no new clinical symptoms, and serum ANCA titer increased only in one patient. All the patients received standard immunosuppressive treatment but eventually died. CONCLUSIONS: Lung cancer is uncommon in patients with GPA; however, the similarity between the imaging findings of lung cancer and GPA may pose a diagnostic challenge. Clinicians should be particularly vigilant when treating older patients with an increased risk of cancer, as they are often asymptomatic or have poorly apparent clinical features.
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Granulomatose com Poliangiite , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/complicações , Masculino , Idoso , Evolução Fatal , Feminino , Imunossupressores/uso terapêutico , Pessoa de Meia-IdadeRESUMO
The emergence of targeted therapies in non-small-cell lung cancer (NSCLC), including inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase, has increased the need for robust companion diagnostic tests. Nowadays, detection of actionable variants in exons 18-21 of the EGFR gene by qPCR and direct DNA sequencing is often replaced by next-generation sequencing (NGS). In this study, we evaluated the diagnostic usefulness of targeted NGS for druggable EGFR variants testing in clinical NSCLC material previously analyzed by the IVD-certified qPCR test with respect to DNA reference material. We tested 59 NSCLC tissue and cytology specimens for EGFR variants using the NGS 'TruSight Tumor 15' assay (Illumina) and the qPCR 'cobas EGFR mutation test v2' (Roche Diagnostics). The sensitivity and specificity of targeted NGS assay were evaluated using the biosynthetic and biological DNA reference material with known allelic frequencies (VAF) of EGFR variants. NGS demonstrated a sufficient lower detection limit for diagnostic applications (VAF < 5%) in DNA reference material; all EGFR variants were correctly identified. NGS showed high repeatability of VAF assessment between runs (CV% from 0.02 to 3.98). In clinical material, the overall concordance between NGS and qPCR was 76.14% (Cohen's Kappa = 0.5933). The majority of discordant results concerned false-positive detection of EGFR exon 20 insertions by qPCR. A total of 9 out of 59 (15%) clinical samples showed discordant results for one or more EGFR variants in both assays. Additionally, we observed TP53 to be a frequently co-mutated gene in EGFR-positive NSCLC patients. In conclusion, targeted NGS showed a number of superior features over qPCR in EGFR variant detection (exact identification of variants, calculation of allelic frequency, high analytical sensitivity), which might enhance the basic diagnostic report.
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Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares , Mutação , Reação em Cadeia da Polimerase em Tempo Real , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Sensibilidade e Especificidade , Éxons/genéticaRESUMO
AIMS: Thymic epithelial tumours (TET), including thymomas and thymic carcinomas and thymic neuroendocrine neoplasms, are malignant neoplasms that can be associated with morbidity and mortality. Recently, an updated version of the World Health Organization (WHO) Classification of Thoracic Tumours 5th Edition, 2021 has been released, which included various changes to the classification of these neoplasms. In addition, in 2017 the Union for International Cancer Control (UICC) / American Joint Committee on Cancer (AJCC) published the 8th Edition Staging Manual which, for the first time, includes a TNM staging that is applicable to thymomas, thymic carcinomas, and thymic neuroendocrine neoplasms. METHODS AND RESULTS: To standardize reporting of resected TET and thymic neuroendocrine neoplasms the accrediting bodies updated their reporting protocols. The International Collaboration on Cancer Reporting (ICCR), which represents a collaboration between various National Associations of Pathology, updated its 2017 histopathology reporting guide on TET and thymic neuroendocrine neoplasms accordingly. This report will highlight important changes in the reporting of TET and thymic neuroendocrine neoplasms based on the 2021 WHO, emphasize the 2017 TNM staging, and also comment on the rigour and various uncertainties for the pathologist when trying to follow that staging. CONCLUSION: The ICCR dataset provides a comprehensive, standardized template for reporting of resected TET and thymic neuroendocrine neoplasms.
Assuntos
Neoplasias Epiteliais e Glandulares , Tumores Neuroendócrinos , Timoma , Neoplasias do Timo , Humanos , Timoma/patologia , Neoplasias do Timo/patologia , Neoplasias Epiteliais e Glandulares/patologia , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologiaRESUMO
Primary mediastinal large B-cell lymphoma (PMBL) cells depend on the constitutive activity of NF-κB and STAT transcription factors, which drive expression of multiple molecules essential for their survival. In a molecularly related B-cell malignant tumor (classic Hodgkin lymphoma), tumor Reed-Sternberg cells overexpress oncogenic (proviral integration site for Moloney murine leukemia virus (PIM) 1, 2, and 3 kinases in a NF-κB- and STAT-dependent manner and PIMs enhance survival and expression of immunomodulatory molecules. Given the multiple overlapping characteristics of Reed-Sternberg and PMBL cells, we hypothesized that PIM kinases may be overexpressed in PMBL and involved in PMBL pathogenesis. The expression of PIM kinases in PMBL diagnostic biopsy specimens was assessed and their role in survival and immune escape of the tumor cells was determined. PIMs were abundantly expressed in primary tumors and PMBL cell lines. Inhibition of PIM kinases was toxic to PMBL cells, attenuated protein translation, and down-regulated NF-κB- and STAT-dependent transcription of prosurvival factors BCL2A1, BCL2L1, and FCER2. Furthermore, PIM inhibition decreased expression of molecules engaged in shaping the immunosuppressive microenvironment, including programmed death ligand 1/2 and chemokine (C-C motif) ligand 17. Taken together, our data indicate that PIMs support PMBL cell survival and immune escape and identify PIMs as promising therapeutic targets for PMBL.
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Janus Quinase 1/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Neoplasias do Mediastino/patologia , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Fator de Transcrição STAT3/metabolismo , Evasão Tumoral , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Janus Quinase 1/genética , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/metabolismo , Neoplasias do Mediastino/imunologia , Neoplasias do Mediastino/metabolismo , NF-kappa B/genética , Proteínas Proto-Oncogênicas c-pim-1/genética , Fator de Transcrição STAT3/genética , Células Tumorais CultivadasRESUMO
We present a case of a 52-year-old man with myasthenia gravis and a mediastinal tumor who was admitted to our hospital for surgical treatment. The pathologic examination of the resected tumor revealed a very rare case of a collision tumor: a B1B2 thymoma and a small lymphocytic lymphoma. Flow cytometry of the peripheral blood revealed the presence of a small number of leukemic cells. After postoperative irradiation of the mediastinum and chemotherapy a complete response in both diseases was achieved. The case confirms that a pathologist should always be aware that two different neoplasms can coexist in rare cases.
Assuntos
Leucemia Linfocítica Crônica de Células B/patologia , Neoplasias Primárias Múltiplas/patologia , Timoma/patologia , Neoplasias do Timo/patologia , Biomarcadores Tumorais/análise , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Primary pulmonary angiosarcoma (PPA) is a rare tumour arising from arterial or venous pulmonary vessels of various size. It is characterized by aggressive course and poor prognosis. The early diagnosis is difficult due to diverse clinical and radiological manifestations. We present a case report of 70 year-old man, active cigarette-smoker, with a 2-month history of non-massive hemoptysis. The thorax CT revealed several solid pulmonary nodules surrounded by areas of ground glass opacity. As bronchoscopy failed to deliver adequate tissue samples, video assisted thoracic surgery (VATS) with pleura and lung biopsy was necessary. Histopathological findings were consistent with pulmonary angiosarcoma. Since no extrapulmonary lesions were demonstrated, the final diagnosis of primary pulmonary angiosarcoma was made. The patient died three months after the onset of symptoms. Our case report highlights that differential diagnosis in patients with hemoptysis and pulmonary nodules should include primary pulmonary sarcoma.
Assuntos
Hemangiossarcoma/diagnóstico , Hemoptise/etiologia , Neoplasias Pulmonares/diagnóstico , Idoso , Diagnóstico Diferencial , Evolução Fatal , Hemangiossarcoma/complicações , Hemangiossarcoma/diagnóstico por imagem , Hemoptise/diagnóstico por imagem , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Fumar , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios XRESUMO
Leflunomide is a disease-modifying anti-rheumatic drug that is used in patients with rheumatoid arthritis (RA), who do not respond well to standard RA treatment. Leflunomide therapy may, however, be related with significant pulmonary complications in predisposed individuals. We present a patient with RA treated with leflunomide, in whom leflunomide lung injury had a fatal outcome. Potential risk factors for pulmonary complications of leflunomide treatment and the management of patients with leflunomide lung injury are discussed.
Assuntos
Adjuvantes Imunológicos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Isoxazóis/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/diagnóstico , Adjuvantes Imunológicos/administração & dosagem , Evolução Fatal , Humanos , Isoxazóis/administração & dosagem , Leflunomida , Masculino , Pessoa de Meia-Idade , Radiografia TorácicaRESUMO
Pulmonary alveolar proteinosis is a very rare interstitial lung disease caused by abnormal intra-alveolar surfactant accumulation. Usually, it appears as a "crazy-paving" pattern on high-resolution computed tomography. The image is so typical, that together with the characteristic bronchoalveolar lavage examination with presence of Periodic Acid Schiff positive substance is sufficient for establishing diagnosis, without histological confirmation. We present the case of the young woman with severe dyspnoea suspected of acute hypersensitivity pneumonia. The computed tomography showed numerous intralobular nodules uniformly distributed troughout the lungs. Treatment by corticosteroids had no clinical effect and next computed tomography showed progression. Despite the high risk of complications (patient had a respiratory failure), a surgical lung biopsy was performed and the histopathological diagnosis of pulmonary alveolar proteinosis was made. The whole lung lavage procedure performed twice caused regression of radiological lesions and respiratory failure.
Assuntos
Macrófagos Alveolares/patologia , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Proteinose Alveolar Pulmonar/terapia , Adulto , Lavagem Broncoalveolar/métodos , Tosse/etiologia , Feminino , Humanos , Hipóxia/etiologia , Pulmão/diagnóstico por imagem , Radiografia Torácica , Tomografia Computadorizada por Raios XRESUMO
Actinomycosis is a rare, chronic infectious disease caused by anaerobic Gram-positive bacteria Actinomyces spp. They induces suppurative inflammation in tissues. They live as commensals in the oropharynx, interstitial tract and genital mucosa, causing almost exclusively endogenic infections. Beacause variable clinical course, its chronicity, quite often actinomycosis mimics rather neoplasmatic disease than infection. We present the case of 56-year old male with unusual pulmonary actinomycosis manifestation as bilateral disseminated lung nodules with systemic symptoms, after initial antitubercular treatment. Diagnosis definitely was made of histologic evaluation of lung specimen from surgical biopsy. After 7-month antibacterial treatment we have achived clinical and radiological improvement.
Assuntos
Actinomicose/diagnóstico , Actinomicose/patologia , Pneumopatias/diagnóstico , Pneumopatias/patologia , Actinomicose/cirurgia , Biópsia , Doença Crônica , Diagnóstico Diferencial , Humanos , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Tuberculose/diagnósticoRESUMO
Here we present a 65-year old ex-smoker with history of recent surgery for vocal cord tumor (histology: moderate grade intraepithelial neoplasia), who reported to the pulmonary outpatient clinic for the nodular lesions in the left lung seen on chest X-ray. Subsequent chest CT scan revealed focal lesion of 18 mm in diameter with spicular margins located in the right upper lobe, another irregular cyst with septa, 62 × 58 mm in the right lower lobe, and calcified nodule in the left lung, no enlarged lymph nodes or pleural effusion was seen. He underwent upper right lobe resection and wedge resection of the lower right lobe. Histological examination revealed adenocarcinoma in the right upper lobe with lymph node metastasis (pT2aN2M0). Examination of the right lower lobe showed squamous cell carcinoma (pT2bN0M0). He was subsequently treated with adjuvant chemotherapy and radiotherapy. During 20 months of the follow-up, he remained in good health with no signs of the disease progression. Patients with synchronous multiple primary lung cancers have significantly less favorable outcome than those with single primary lung malignancies, although it can be considerably improved with radical surgical treatment. Basing on the above case report, we discussed diagnostic and therapeutical scheme in patients with the primary multiple lung cancers, and have analyzed epidemiological data and some aspects of MPM etiology.
Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Idoso , Seguimentos , Humanos , Masculino , Resultado do TratamentoRESUMO
INTRODUCTION: In recent years, positron emission tomography (PET) has been increasingly applied in the diagnosis of neoplastic lung diseases. In contrast to conventional imaging studies, PET-CT enables the visualisation of not only the morphology of the suspicious lesion, but also its metabolism. The aim of the present study was to investigate the role of PET-CT in the initial assessment of patients with indeterminate solitary pulmonary lesions. MATERIAL AND METHODS: The study was conducted on a group of 82 patients with indeterminate lung nodule diagnosed at the National Institute of Tuberculosis and Lung Diseases in the period from January 2008 to May 2011. CT and PET-CT were performed in all of the patients. Histological or cytological examination of the biopsy specimens obtained from bronchoscopy, mediastinoscopy and intraoperatively were the reference tests. RESULTS: Malignancy was documented in 40 patients (48.8%). Histopathological analysis of all tumours revealed 12 cases of squamous cell carcinoma, 18 cases of adenocarcinoma and 1 case of carcinoid, whereas in 9 patients the diagnosis of "non-small cell cancer not otherwise specified" was made. All lesions except one were of solid character on chest CT. SUV(max) values exceeding 2.5 were found in 38 cancer patients (true positives, TP). The mean value of SUV(max) was 9.1 (1-26.8). Forty-two lesions were documented as benign (51.2%). SUV(max) values equal to or less than 2.5 were found in 37 patients (true negatives, TN). The mean value of SUV(max) in this group was 1.9 (0.5-8.6). The diagnostic value of PET-CT SUV(max) exceeding 2.5 in the prediction of neoplastic origin of solitary pulmonary lesions was: sensitivity - 95% (95% CI 84-99%), specificity - 88% (95% CI 75-95%) and accuracy - 91.5% (95% CI 83-96%). Positive predictive value (PPV) was 88.4% (95% CI 76-95%), and negative predictive value (NPV) was 94.8% (95% CI 83-99%). False negative results concerned two patients, with final diagnosis of carcinoid and adenocarcinoma; false positive results were obtained in 5 patients with various inflammatory lesions. CONCLUSIONS: In the present study, PET-CT appeared to have high sensitivity (95%), but lower specificity (88%) for predicting the malignant character of solitary pulmonary lesions. Overall diagnostic value of PET-CT SUV(max) > 2.5 was high - PPV was 88.4%, NPV was 94.8%. In the authors' opinion, the PET-CT value may increase when clinical data as well as other radiological documentation (with retrospective assessment) are taken into consideration.
Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico por imagem , Adulto , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Nódulo Pulmonar Solitário/patologia , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Pathologists are staging thymic epithelial tumors (TET) according to the 8th UICC/AJCC TNM system. Within the French RYTHMIC network, dedicated to TET, agreement on pathologic tumor stage (pT) among the pathology panelists was difficult. The aim of our study was to determine the interobserver reproducibility of pT at an international level, to explore the source of discrepancies and potential interventions to address these. METHODS: An international panel of pathologists was recruited through the International Thymic Malignancy Interest Group (ITMIG). The study focused on invasion of mediastinal pleura, pericardium, and lung. From a cohort of cases identified as challenging within the RYTHMIC network, we chose a series of test and validation cases (n = 5 and 10, respectively). RESULTS: Reproducibility of the pT stage was also challenging at an international level as none of the 15 cases was classified as the same pT stage by all ITMIG pathologists. The agreement rose from slight (κ = 0.13) to moderate (κ = 0.48) between test and validation series. Discussion among the expert pathologists pinpointed two major reasons underlying discrepancies: 1) Thymomas growing with their "capsule" and adhering to the pleurae, pericardium, or lung were often misinterpreted as invading these structures. 2) Recognition of the mediastinal pleura was identified as challenging. CONCLUSION: Our study underlines that the evaluation of the pT stage of TET is problematic and needs to be addressed in more detail in an upcoming TNM classification. The publication of histopathologic images of landmarks, including ancillary tests could improve reproducibility for future TNM classifications.
Assuntos
Neoplasias Pulmonares , Neoplasias Epiteliais e Glandulares , Neoplasias do Timo , Humanos , Reprodutibilidade dos Testes , Neoplasias do Timo/diagnóstico , Neoplasias Epiteliais e Glandulares/diagnósticoRESUMO
Metaplastic thymoma (MT), a rare subtype of thymic epithelial tumors (TETs), harbors YAP1::MAML2 fusions. Poroma, a skin tumor, also carries these fusions and exhibits a unique staining pattern for YAP1 immunohistochemistry (IHC), namely, a YAP1 N-terminus (YAP1[N])-positive but YAP1 C-terminus (YAP1[C])-negative pattern. In this context, MT was recently reported to lack YAP1(C) expression exclusively among TET subtypes. However, a lack of information about YAP1(N) expression in that study and another report that wild-type YAP1 expression was diminished in type B3 thymoma and thymic carcinoma warrants further studies for YAP1 expression in TETs. Thus, we immunohistochemically examined YAP1(N) and YAP1(C) staining patterns in our TET samples, including 14 cases of MT. In addition, 11 of the 14 MT cases were genetically analyzed with the formalin-fixed paraffin-embedded tissues if they harbored YAP1::MAML2 fusions. MT consistently exhibited YAP1(N)-positive and YAP(C)-negative staining, whereas type B3 thymoma and thymic carcinoma showed relatively heterogeneous staining patterns for YAP1(N) and YAP1(C) and were sometimes negative for both antibodies. Furthermore, a lower expression of YAP1 was found in type B3 compared to B2 thymomas. Among genetically analyzed 11 MT cases, 6 cases showed YAP1::MAML2 fusions, whereas the analysis failed in 5 very old cases due to poor RNA quality. These results indicate that IHC of both YAP1(N) and YAP1(C) is recommended to obtain staining patterns almost unique to MT. The biological significance of YAP1 in high-grade TETs warrants further investigation.
Assuntos
Neoplasias Laríngeas/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Linfangioma/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Papiloma/complicações , Infecções por Papillomavirus/diagnóstico por imagem , Adulto , Dor no Peito/etiologia , Dispneia/etiologia , Feminino , Hemoptise/etiologia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Linfangioma/complicações , Linfangioma/patologia , Imageamento por Ressonância Magnética , Neoplasias Primárias Múltiplas/complicações , Neoplasias Primárias Múltiplas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Derrame Pleural/etiologiaRESUMO
INTRODUCTION: Non-small cell lung cancer (NSCLC) has become the leading cause of cancer-related deaths in Poland. Follow-up of patients with NSCLC is aimed at early detection of local recurrence, metastatic process, treatment-related complications or second primary lung cancer. We investigated the diagnostic accuracy of FDG-PET-CT in the detection of recurrence of NSCLC after treatment. MATERIAL AND METHODS: Seventy-two NSCLC patients (19 females, 56 males), stage I to IV, who had undergone surgery and/ /or radiation therapy, occasionally associated with chemotherapy, were retrospectively included in our study. Chest radiographs and thoracic computed tomography (CT) were performed to localize the abnormality prior to PET-CT. All the patients underwent CT and PET-CT in the period from January 2008 until January 2012. All PET images were interpreted in conjunction with thoracic CT. PET-CT and CT diagnoses were correlated with pathological diagnoses. RESULTS: Forty-five patients had recurrent tumour. Tumour recurrence was observed more often in men than in women and also in case of neoplastic cell emboli in lymphatic or blood vessels. In three patients second primary lung cancer was diagnosed. False positive diagnosis of relapse based on PET-CT was obtained in 4 patients, mainly due to inflammatory lesions. The accuracy of PET-CT for diagnosis of recurrence was 94.4% (95% CI 91; 100). CONCLUSIONS: FDG PET-CT was the best method to differentiate recurrent bronchogenic carcinoma from inflammatory lesions, especially at post-therapeutic sites. It has been shown that PET-CT is more accurate method than CT in recurrent NSCLC. PET-CT results had a further impact on the clinical management and treatment planning.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/diagnóstico por imagem , Segunda Neoplasia Primária/diagnóstico , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Lung cancer is the most frequent malignant tumour in men. Advanced disease may produce metastatic tumours in subcutaneous tissue and also infiltrate the chest wall. We present a history of a man referred to our department suspected of lung tumour infiltrating the chest wall. Additionally, bone metastatic disease was diagnosed (ribs, vertebral bodies and skull). Thanks to a wide diagnostic approach, ductal cancer of the breast was finally diagnosed, a neoplasm that is extremely rare in male patients, usually presenting as a definite nodule in the nipple area of the breast. This case shows the importance of careful histological evaluation of the chest wall tumour.
Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/patologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/secundário , Neoplasias Torácicas/diagnóstico , Idoso , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/patologia , Carcinoma Ductal de Mama/patologia , Diagnóstico Diferencial , Humanos , Masculino , Neoplasias Torácicas/patologia , Parede TorácicaRESUMO
A better understanding of the molecular pathogenesis of thymic epithelial tumours (TETs) could revolutionise their treatment. We evaluated thymomas and thymic carcinomas by next-generation sequencing (NGS) of somatic or germline single nucleotide variants (SNVs) in genes commonly mutated in solid tumours. In total, 19 thymomas and 34 thymic carcinomas were analysed for nonsynonymous SNVs in 15 genes by targeted NGS (reference genome: hg19/GRCh37). Ten SNVs in TP53 (G154V, R158P, L194H, R267fs, R273C, R306 *, Q317 *), ERBB2 (V773M), KIT (L576P), and KRAS (Q61L) considered somatic and pathogenic/likely pathogenic were detected in 10 of 34 (29.4%) thymic carcinomas. No somatic SNVs confirmed as pathogenic/likely pathogenic were found in thymomas. Rare SNVs of uncertain or unknown functional and clinical significance, to our knowledge not reported previously in TETs, were found in ERBB2 (S703R), KIT (I690V), and FOXL2 (P157S) in 3 of 19 (16%) thymomas. The most frequent germline SNVs were TP53 P72R (94% TETs), ERBB2 I655V (40% TETs), and KIT M541L (9% TETs). No significant difference in median disease-free survival (DFS) was found between thymic carcinoma patients with and without pathogenic SNVs (p = 0.190); however, a trend toward a longer DFS was observed in the latter (16.0 vs. 30.0 months, respectively). In summary, NGS analysis of TETs revealed several SNVs in genes related to the p53, AKT, MAPK, and K-Ras signalling pathways. Thymic carcinomas showed greater genetic dysregulation than thymomas. The germline and rare SNVs of uncertain clinical significance reported in this study add to the number of known genetic alterations in TETs, thus extending our molecular understanding of these neoplasms. Druggable KIT alterations in thymic carcinomas have potential as therapeutic targets.
RESUMO
Background: Thymomas are characterized by a low tumor mutation burden and a paucity of actionable mutations. Clinical behavior can vary from relatively indolent to very aggressive and impact survival. Platinum-based chemotherapy is the primary treatment modality for inoperable disease and is palliative in intent. Patients with advanced thymoma frequently experience disease recurrence after frontline therapy. Treatment options for relapsed thymoma are relatively limited. A case of recurrent thymoma harboring a breast cancer gene 2 (BRCA2) mutation was presented for multidisciplinary discussion at the International Thymic Malignancy Interest Group (ITMIG) Tumor Board meeting. Case Description: A 63-year-old female presented with Tumor Node Metastasis (TNM) stage I, World Health Organization (WHO) subtype B1 thymoma at diagnosis and underwent surgical resection. First recurrence occurred in the left costophrenic recess and was treated with preoperative external beam radiotherapy (EBRT), surgical excision, and post-operative chemotherapy. Histology was consistent with WHO subtype B2 thymoma and genomic analysis of the resected tumor detected a BRCA2 mutation. Second recurrence occurred in the mediastinum and bilateral pleurae. Mediastinal disease was treated with EBRT, and the pleural deposits were observed initially. However, upon further progression, the case was discussed at the ITMIG tumor board meeting to determine optimal second line therapy for this patient. Conclusions: A potential role of poly (ADP-ribose) polymerase (PARP) inhibitors versus cytotoxic chemotherapy for treatment of BRCA2-mutated recurrent thymoma merits discussion. However, due to the absence of data to support the functional and therapeutic significance of BRCA2 mutations in patients with thymoma, the potential for severe toxicity associated with PARP inhibitors, and availability of other safe and effective alternatives, other treatment options should be considered. PARP inhibitors can be considered for treatment of BRCA2-mutated thymomas as part of a clinical trial or when other treatment options have been exhausted.
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Thymic mucoepidermoid carcinoma (MEC) is a rare tumor, and its characteristics remain to be clarified. Here we investigated 20 cases of thymic MEC to systematically characterize its clinical, histopathologic, and molecular features. The median age of the patients was 56 years (range, 19 to 80 y), there was a slight male predilection (3:2), and 44% of the patients were asymptomatic at diagnosis. The median tumor size was 6.8 cm in diameter, 55% were pT1 tumors, and 50% were TNM stage I tumors. When 4 tumor grading systems for salivary MEC (Armed Forces Institutes of Pathology, Brandwein, modified Healey, and the Memorial Sloan-Kettering) were employed, low-grade, intermediate-grade, and high-grade tumors accounted for 35% to 70%, 5% to 25%, and 25% to 50%, respectively. Many histologic variants were noted, and 70% of the cases were classified as nonclassic variants. MAML2 rearrangement was detected in 56% of cases, and the fusion partner was CRTC1 in all cases. CRTC1-MAML2 fusion was associated with lower pT classification and lower TNM stage. The overall survival rate of all patients was 69% and 43% at 5 and 10 years, respectively. Worse overall survival was associated with higher pT stage, higher TNM stage, residual tumors, greater tumor size, high-grade tumor histology (Armed Forces Institutes of Pathology and Memorial Sloan-Kettering, but not the other 2), and with the absence of CRTC1-MAML2 fusion. Of note, none of the patients with CRTC1-MAML2 fusion-positive tumors died during the follow-up. In conclusion, the clinicopathologic and molecular findings of thymic MEC presented here are expected to contribute to the management of this rare tumor.
Assuntos
Carcinoma Mucoepidermoide , Neoplasias das Glândulas Salivares , Timoma , Neoplasias do Timo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Mucoepidermoide/patologia , Proteínas de Ligação a DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares , Proteínas de Fusão Oncogênica , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/terapia , Neoplasias do Timo/genética , Neoplasias do Timo/terapia , Transativadores , Fatores de Transcrição , Adulto JovemRESUMO
Thymic carcinomas are rare malignancies that in general arise in the prevascular (anterior) mediastinum. These tumors are usually invasive, often present at advanced stages, and typically behave aggressively. Studies are hampered by the paucity of these tumors, the large variety of carcinoma subtypes, and the lack of unique morphologic and immunophenotypic features. Despite these challenges, advances in diagnostic imaging, surgical approaches, systemic therapies, and radiation therapy techniques have been made. The WHO classification of thymic epithelial tumors has been updated in 2021, and the eighth tumor nodal metastasis staging by the American Joint Committee on Cancer/Union for International Cancer Control included thymic carcinomas in 2017. Molecular alterations that provide more insight into the pathogenesis of these tumors and that potentially permit use of novel targeted therapies are increasingly being identified. New approaches to radiation therapy, chemotherapy, and immunotherapy are under evaluation. International societies, including the International Thymic Malignancy Interest Group, European Society of Thoracic Surgeons, and Japanese, Chinese, and Korean thymic associations, have been critical in organizing and conducting multi-institutional clinical studies. Herein, we review contemporary multidisciplinary perspectives in diagnosis and management of thymic carcinoma.