Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment / 北京大学学报(医学版)

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.

The value and related complications of lymph node dissection along bilateral recurrent laryngeal nerves in esophageal cancer patients / 中华肿瘤杂志

Esophageal cancer is one of the most common malignant tumors of digestive tract, lymph node metastasis is a frequently encountered metastasis in the esophageal cancer patients. The number of lymph node metastasis is reported as an important prognostic factor, and it also affects the choice of postoperative treatments in the esophageal cancer. It was reported that the recurrent laryngeal nerve lymph nodes are the most common sites of nodal metastasis and need to be completely dissected during the esophagectomy for thoracic esophageal cancers. Dissection of the lymph nodes along bilateral recurrent laryngeal nerves not only improves the accuracy of staging, but also improves postoperative survival of esophageal cancer patients due to reducing the local recurrence. However, it also brings problems such as injury of laryngeal recurrent nerves, and increases postoperative complications such as pulmonary complications and malnutrition due to aspiration and coughing. Therefore, it is necessary to preserve the structure and function of bilateral recurrent laryngeal nerves during esophagectomy through careful manipulations, and minimize the impact of complications in prognosis and quality of life from injury to the recurrent laryngeal nerve.

Thoracic calcifications on magnetic resonance imaging: correlations with computed tomography / Calcificações torácicas na ressonância magnética: correlações com a tomografia computadorizada

ABSTRACT Objective: To identify the characteristics of thoracic calcifications on magnetic resonance (MR) imaging, as well as correlations between MR imaging and CT findings. Methods: This was a retrospective study including data on 62 patients undergoing CT scans and MR imaging of the chest at any of seven hospitals in the Brazilian states of Rio Grande do Sul, São Paulo, and Rio de Janeiro between March of 2014 and June of 2016 and presenting with calcifications on CT scans. T1- and T2-weighted MR images (T1- and T2-WIs) were semiquantitatively analyzed, and the lesion-to-muscle signal intensity ratio (LMSIR) was estimated. Differences between neoplastic and non-neoplastic lesions were analyzed. Results: Eighty-four calcified lesions were analyzed. Mean lesion density on CT was 367 ± 435 HU. Median LMSIRs on T1- and T2-WIs were 0.4 (interquartile range [IQR], 0.1-0.7) and 0.2 (IQR, 0.0-0.7), respectively. Most of the lesions were hypointense on T1- and T2-WIs (n = 52 [61.9%] and n = 39 [46.4%], respectively). In addition, 19 (22.6%) were undetectable on T1-WIs (LMSIR = 0) and 36 (42.9%) were undetectable on T2-WIs (LMSIR = 0). Finally, 15.5% were hyperintense on T1-WIs and 9.5% were hyperintense on T2-WIs. Median LMSIR was significantly higher for neoplastic lesions than for non-neoplastic lesions. There was a very weak and statistically insignificant negative correlation between lesion density on CT and the following variables: signal intensity on T1-WIs, LMSIR on T1-WIs, and signal intensity on T2-WIs (r = −0.13, p = 0.24; r = −0.18, p = 0.10; and r = −0.16, p = 0.16, respectively). Lesion density on CT was weakly but significantly correlated with LMSIR on T2-WIs (r = −0.29, p < 0.05). Conclusions: Thoracic calcifications have variable signal intensity on T1- and T2-weighted MR images, sometimes appearing hyperintense. Lesion density on CT appears to correlate negatively with lesion signal intensity on MR images.

RESUMO Objetivo: Identificar as características das calcificações torácicas na ressonância magnética (RM) e as correlações entre os achados de RM e TC. Métodos: Estudo retrospectivo no qual foram analisados dados referentes a 62 pacientes que foram submetidos a TC e RM de tórax em sete hospitais nos estados do Rio Grande do Sul, São Paulo e Rio de Janeiro entre março de 2014 e junho de 2016 e que apresentaram calcificações na TC. As imagens de RM ponderadas em T1 e T2 (doravante denominadas T1 e T2) foram analisadas semiquantitativamente, e a razão entre a intensidade do sinal da lesão e do músculo (LMSIR, do inglês lesion-to-muscle signal intensity ratio) foi estimada. Diferenças entre lesões neoplásicas e não neoplásicas foram analisadas. Resultados: Foram analisadas 84 lesões calcificadas. A média de densidade das lesões na TC foi de 367 ± 435 UH. A mediana da LMSIR foi de 0,4 [intervalo interquartil (II): 0,1-0,7] em T1 e 0,2 (II: 0,0-0,7) em T2. A maioria das lesões mostrou-se hipointensa em T1 e T2 [n = 52 (61,9%) e n = 39 (46,4%), respectivamente]. Além disso, 19 (22,6%) foram indetectáveis em T1 (LMSIR = 0) e 36 (42,9%) foram indetectáveis em T2 (LMSIR = 0). Finalmente, 15,5% mostraram-se hiperintensas em T1 e 9,5% mostraram-se hiperintensas em T2. A mediana da LMSIR foi significativamente maior nas lesões neoplásicas do que nas não neoplásicas. Houve uma correlação negativa muito fraca e estatisticamente insignificante entre a densidade das lesões na TC e as seguintes variáveis: intensidade do sinal em T1, LMSIR em T1 e intensidade do sinal em T2 (r = −0,13, p = 0,24; r = −0,18, p = 0,10 e r = −0,16, p = 0,16, respectivamente). A densidade das lesões na TC apresentou correlação fraca, porém significativa com a LMSIR em T2 (r = −0,29, p < 0,05). Conclusões: As calcificações torácicas apresentam intensidade de sinal variável em T1 e T2; em alguns casos, mostram-se hiperintensas. A densidade da lesão na TC aparentemente correlaciona-se negativamente com a intensidade do sinal da lesão na RM.

Tumours of the Chest in Children: A Review

Tumours of the chest in children constitute an array of pathology and clinical symptomatology. These tumours can be benign or malignant; cystic or solid; primary or as a result of secondary metastases. Collectively; tumours of the chest in children are very rare; the exact incidence of which is largely unknown globally. Non neoplastic lesions of the lung including bronchogenic cysts; sequestrations; congenital pulmonary airway malformations as well as infective and inflammatory disorders are 60 times more common than neoplastic causes.1 A tumour of the chest is considerably difficult to diagnose since patients can be asymptomatic for many years before symptoms evolve. Even more so; the symptoms are non-specific and can suggest more common and less sinister pathology. Clinically patients present with a variety of symptoms that depend largely on the location of the tumour.Airway tumours can be symptomatic or can present with chronic cough; wheeze; haemoptysis; atelectasis or persistent pneumonia. Secondary malignant parenchymal tumours are likely to be symptomatic from the primary lesion. Anterior mediastinal tumours can cause compression of the large airways or superior vena caval structures.It stands to reason that the physician needs to have a very high index of suspicion when dealing with these non-specific signs and symptoms. This article provides an approach to tumours of chest and reviews the common aetiology in the different compartments of the chest. The article will focus on common tumours of the airway; lung parenchyma; mediastinum; cardiac and chest wall pathology

Schwannoma intratorácico / Intrathoracic schwannoma

El schwannoma (neurilemoma) es un tumor benigno de lento crecimiento originado en la vaina de Schwann, cuya localización en la cavidad torácica es excepcional. En general es asintomático y se descubre en forma incidental, aunque puede ocasionar síntomas cuando la lesión crece o invade estructuras subyacentes. Su importancia radica en la posibilidad de confusión con tumores malignos. Presentamos una paciente con dolor torácico de evolución prolongada causado por un schwannoma. La imagen tomográfica es sugestiva de tumor extrapulmonar, por ello el schwannoma en esta localización debe ser considerado en el diagnóstico diferencial de tumores pleurales metastásicos o primarios como el lipoma, el tumor fibroso solitario y el mesotelioma.

The schwannoma (neurilemmoma) is a slow-growing benign tumor originating from Schwann sheath whose location in the chest cavity is exceptional. It is generally asymptomatic and is discovered incidentally but can cause symptoms when the lesion grows or invade underlying structures. Its importance lies in the possibility of confusion with malignant tumors. We present a patient who complains of chest pain caused by a prolonged course schwannoma. The tomographic image is suggestive of extrapulmonary tumor, so the schwannoma in this location should be considered in the differential diagnosis of metastatic or primary pleural tumors such as lipoma, solitary fibrous tumor and mesothelioma.

Clinical Value of Endobronchial Ultrasound Findings for Predicting Nodal Metastasis in Patients with Suspected Lymphadenopathy: A Prospective Study

We evaluated whether sonographic findings can provide additional diagnostic yield in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), and can more accurately predict nodal metastasis than chest computed tomography (CT) or positron emission tomography (PET)/CT scans. EBUS-TBNA was performed in 146 prospectively recruited patients with suspected thoracic lymph node involvement on chest CT and PET/CT from June 2012 to January 2013. Diagnostic yields of EBUS finding categories as a prediction model for metastasis were evaluated and compared with findings of chest CT, PET/CT, and EBUS-TBNA. In total, 172 lymph nodes were included in the analysis: of them, 120 were malignant and 52 were benign. The following four EBUS findings were predictive of metastasis: nodal size > or =10 mm, round shape, heterogeneous echogenicity, and absence of central hilar structure. A single EBUS finding did not have sufficient diagnostic yield; however, when the lymph node had any one of the predictive factors on EBUS, the diagnostic yields for metastasis were higher than for chest CT and PET/CT, with a sensitivity of 99.1% and negative predictive value of 83.3%. When any one of predictive factors is observed on EBUS, subsequent TBNA should be considered, which may provide a higher diagnostic yield than chest CT or PET/CT.

Giant chondrosarcoma of chest wall.

Primary chest wall tumours are very rare. Chondrosarcoma is the most common tumour arising from the chest wall. We describe the occurrence of a slow-growing chondrosarcoma arising from the anterior chest wall in a 35-year-old male patient. The tumour was resected successfully and chest wall was reconstucted with prolene mesh and muscle flap. The patient was discharged uneventfully without any respiratory compromise. There was no recurrence after a three-year follow-up. Wide surgical resection with chest wall reconstruction appears to be the preferred treatment option for this rare tumour of the chest wall.

Chest wall metastasis of squamous cell carcinoma of larynx.

Distant metastases in squamous cell carcinoma of head and neck are most often to the lung, liver and bone. They rarely metastasise to chest wall. We report a 60-year-old male patient who initially presented with an abscess over the anterior chest wall that was initially treated for infective pathology. Due to lack of response, cytological examination was performed that turned out to be metastasis from carcinoma larynx.

Multiple myeloma presenting with multiple thoracic manifestations.

Multiple myeloma is a malignant proliferation of plasma cells that affects mainly bone marrow but may also involve other organs as well. We report thoracic involvement in the form of left-sided pleural effusion, osseous lesions, bronchial infiltration, and mediastinal lymphadenopathy in a 61-year-old woman, non-smoker presented with chest pain, dyspnoea, cough and deterioration in general health over the preceding seven months. Immunoelectrophoresis and immunofixation showed raised kappa-light chain immunoglobulin G (IgG) in serum and pleural fluid. Bronchial and pleural biopsies documented myelomatous infiltration and bone marrow aspirate revealed extensive plasma cell infiltration. At eight months, following the fourth cycle of melphalan, endoxan and prednisone based chemotherapy, the patient died.

Computed tomography guided percutaneous transthoracic fine needle aspiration cytology in chest masses.

A retrospective, hospital based descriptive study was done to know the pathological spectrum of thoracic lesions and to correlate the radiological findings with cytological findings obtained from computed tomography guided percutaneous transthoracic fine needle aspiration of chest mass. The clinical, radiological and cytological data of 100 patients were studied who underwent CT guided FNAC from May, 2004 to May, 2007. Diagnostic accuracy of FNAC is 82%. Cytological examination showed that 51 cases were malignant and 31 cases were benign. Provisional diagnosis based on radiological findings were 50 and 32 cases of malignant and benign lesions respectively. Sensitivity and specificity, positive and negative predictive value of radiological findings in this study was 88%, 84%, 90% and 81% respectively. Post procedure complication were (a) pneumothorax in two cases and both the cases had to be hospitalized for active management (b) minimal perilesional hemorrhage and hemoptysis in three cases and (c) chest pain in six cases. CT guided FNAC is a simple and safe procedure with high diagnostic accuracy in the evaluation of focal chest lesions. Pneumothorax, perilesional hemorrhage, hemoptysis and chest pain are the usually encountered complications. Very few cases of complication require active management.

Valor de la biopsia aspirativa con aguja fina para el diagnóstico de tumores intraabdominales e intratorácicos / Value of fine-needle aspiration biopsy for the diagnosis of intrathoracic and intraabdominal tumors

Introducción. La biopsia aspirativa con aguja fina permite el diagnóstico de enfermedades tan graves como el cáncer en la infancia, en un breve período de tiempo y con gran exactitud. El método se ha establecido como una técnica rápida, efectiva y económica en la biopsia de tumores de cavidades como la abdominal y la torácica. El objetivo de esta investigación fue comprobar la aplicación y validez del método diagnóstico en los tumores intratorácicos e intraabdominales en la infancia. Métodos. En el Hospital Pediátrico ®William Soler¼, se realizó un estudio retrospectivo de las citologías aspirativas realizadas en tumores intratorácicos e intraabdominales entre enero de 1999 y diciembre de 2005. En todas se realizó la técnica de biopsia por aspiración preconizada en Estocolmo y se utilizó también la técnica de citopunción. Resultados. El abdomen fue la región más frecuente, en particular, el riñón. Veinte citologías fueron negativas de malignidad (17,6 por ciento) y 65, positivas (57,5 por ciento). Existió una buena correlación citohistológica positiva. La sensibilidad fue del 96,1 por ciento; el valor predictivo positivo, del 94,9 por ciento y la eficiencia, del 92,8 por ciento. Conclusiones. La biopsia con aguja fina es un método eficaz para el diagnóstico de los tumores intraabdominales e intratorácicos en la infancia. Tiene gran valor diagnóstico para cirujanos, pediatras y oncólogos, y permite planificar de manera eficaz la conducta ulterior ante cada paciente.

Introduction. Fine needle aspiration biopsy allows the diagnosis of diseases as severe as cancer in childhood in a short period of time, and with great accuracy. This method has been established as a rapid, effective and economic technique in the biopsy of tumours of cavities such as the abdominal and the thoracic. The objective of this research was to check the application and validity of the diagnostic method in intrathoracic and intraabdominal tumours in children. Methods: A retrospective study of the aspiration cytologies performed in intrathoracic and intraabdominal tumours at William Soler Teaching Children Hospital from January 1999 to December 2005 was conducted . In all of them the aspiration biopsy technique recommended in Stockholm was used, and the cytopuncture technique was also applied. Results. The abdomen was the most frequent region and, in particular, the kidney. Twenty cytologies yielded negative (17.6 percent), and 65 positive (57.5 percent). There was a good positive cytohistologic correlation. Sensivity was 96.1 percent; positive predictive value, 94.9 percent; and efficiency, 92.8 percent. Conclusions. Fine needle biopsy is an effective method for the diagnosis of intraabdominal and intrathoracic tumours in children. It has a great diagnostic value for surgeons, pediatricians and oncologists, and it also allows to plan in a efficient way the conduct to be followed with each patient.

Tumores fetales: II parte / Fetal tumors: part II

Se presenta la segunda parte de una revisión resumida de los diferentes tumores fetales, haciendo énfasis en su diagnóstico prenatal y posibles tratamientos intrauterinos. En esta segunda parte se analizan los tumores torácicos, abdominales y misceláneos.

Citopatologia de tumores raros do pulmão e da parede torácica: relato de seis casos / Cytological characteristics of rare thoracic tumors: report of six cases

Sob o ponto de vista citopatológico, existem três grandes tipos de tumores brônquicos: carcinoma de células escamosas, adenocarcinoma e carcinoma de pequenas células, que correspondem em nossa experiência, a mais de 95 dos casos. Os demais tipos citológicos são muito raros, mas sua eventual ocorrência deve ser sempre buscada, pois seu comportamento biológico e respectivo tratamento costumam diferir e necessitam individualização. Neste trabalho, relatamos seis casos de tumores torácicos relativamente raros, com sua respectiva apresentação citopatológica: oncocitoma pulmonar, fibrossarcoma pulmonar, tumor de Askin, mieloma da parede torácica, envolvimento pleuro-pulmonar por linfoma de células T e metástase endobrônquica de carcinoma de endométrio

Solitary calvarial metastases: an unusual presentation of thoracic neuroblastoma.

A primary thoracic origin occurs only in 20% of neuroblastomas, and their classical presentation is mediastinal or cord compression. Skeletal metastases of neuroblastomas are characteristically multiple, and calvarial deposits usually show simultaneous involvement of orbit. Solitary metastases in neuroblastoma, is an unusual entity and its presentation as a large calvarial mass, especially from a thoracic primary, is rare. Furthermore, calvarial metastases are relatively uncommon in children compared to adults. We discuss the clinical, radiographic, CT features, and differential diagnosis of a large calvarial mass with sunray spiculation in a child, which was due to a solitary metastases from an occult thoracic neuroblastoma. The possibility of neuroblastoma presenting in this unique fashion and the importance of considering a chemosensitive tumor such as neuroblastoma in the differential diagnosis of a solitary calvarial mass in a child is highlighted by our report.

Malignant Transformation of Intrathoracic Ancient Neurilemmoma in a Patient without Von Recklinghausen's Disease

Malignant transformation of a neurilemmoma is an exceedingly rare event. We describe a case of intrathoracic ancient neurilemmoma undergoing a malignant change in a 39-yr-old man. The patient presented with right flank and chest pain for several months. Plain radiography and CT scan of the chest showed a soft tissue mass lesion at the extrapleural space with erosion of surrounding ribs at the right basal lung area. The excised mass was encapsulated and measured 4.5 x 3.5 x 2.3 cm. The cut surface showed grayish-white and glistening with a focal cystic change and hemorrhage. Necrosis was not seen. Histologically, the tumor showed the features of classic neurilemmoma composed of the Antoni type A and B areas with perivascular hyalinization. In addition, obviously histo-logically malignant foci manifested by presence of markedly increased cellularity with fascicular arrangement, active mitotic activity, hyperchromasia, and gradual loss of original neurilemmomatous feature were noted.

Computed tomography guided fine needle aspiration cytology in the diagnosis of thoracic lesions.

Computed tomography (CT) allows the performance of fine needle aspiration cytology (FNAC) in situations in which ultrasound or conventional x-rays do not correctly visualise the lesion or the needle tract. Over an 18-month period 184 patients underwent CT-guided FNAC of thoracic lesions. Of these 140 patients presented with pulmonary parenchymal lesions, 18 with mediastinal lesions, 14 with pleural lesions and 12 with hilar lymphadenopathy. A categorical diagnosis was possible in 180 (98%) cases. In majority of the cases only one or two passes were required. Two cases developed pneumothorax and required chest drainage. It can be concluded from the present observations that FNAC under CT control is a useful and accurate diagnostic technique.