RESUMO
While lung cancer is one of the most common malignancies routinely encountered by pathologists, benign pulmonary neoplasms are quite rare. However, it is important for pathologists to be familiar with the typical diagnostic features of benign lung tumors to avoid confusing them with malignant morphological mimics. There have also been intriguing discoveries in the genetics of benign pulmonary neoplasms in the past decade. This review will cover several of the most common benign lung tumors, including the diagnostic categories of pulmonary adenomas, bronchial papillomas, and benign mesenchymal tumors, with discussion of the current classification, differential diagnosis, and current knowledge regarding genetic drivers.
Assuntos
Adenoma , Neoplasias Brônquicas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Brônquicas/patologia , Adenoma/patologiaRESUMO
Most pathologists are well versed in the diagnosis of lung cancer, given the common nature of the disease. Occasionally more unusual neoplasms are encountered in lung biopsies and resections, which may be difficult to distinguish from "run of the mill" lung cancer cases based on overlapping morphologic and immunophenotypic features. The accurate diagnosis of these rare entities is quite challenging and requires careful morphological examination paired with judicious use of ancillary immunohistochemical and genetic studies. Herein, the clinicopathological and genetic features of five unusual lung tumors will be reviewed, including thoracic SMARCA4-deficient undifferentiated tumor, NUT carcinoma, sclerosing pneumocytoma, primary pulmonary myxoid sarcoma/angiomatoid fibrous histiocytoma, and bronchiolar adenoma/ ciliated muconodular papillary tumor. Since recognition of these entities by pathologists is of increasing importance to guide prognosis and therapy, emphasis will be placed on practical tips to reach these rare diagnoses with confidence.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Pulmonares/patologia , Pulmão/patologia , DNA Helicases/genética , Humanos , Neoplasias Pulmonares/genética , Proteínas Nucleares/genética , Prognóstico , Fatores de Transcrição/genéticaRESUMO
Malignant rhabdoid tumor of the kidney (MRTK) is a rare aggressive pediatric renal tumor which can be diagnosed via fine-needle aspiration (FNA) cytology and core biopsy. The diagnosis of MRTK is challenging, and requires morphologic, immunohistochemical and clinical correlation to distinguish it from other entities. The differential diagnosis includes Wilms tumor, desmoplastic small round cell tumor, rhabdomyosarcoma, synovial sarcoma, renal medullary carcinoma, and epithelioid sarcoma. Here we describe a case of MRTK diagnosed on renal cytology and core biopsy with immunohistochemistry and follow by nephrectomy with gross and morphologic findings.
Assuntos
Neoplasias Renais , Tumor Rabdoide , Biomarcadores Tumorais , Criança , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/patologia , Proteína SMARCB1RESUMO
AIMS: Pulmonary chondromas, which are rare cartilaginous neoplasms that often arise in the setting of Carney triad, are morphologically similar to pulmonary hamartomas, which are much more common. There is evidence that succinate dehydrogenase (SDH) deficiency drives neoplasia in patients with Carney triad, and SDHB immunohistochemistry can be used as a surrogate marker to detect SDH deficiency. The aim of this study was to investigate the utility of SDHB immunohistochemistry in distinguishing pulmonary chondromas from hamartomas. METHODS AND RESULTS: Immunohistochemistry for SDHB (clone 21A11AE7) was performed on histological sections from six cases of pulmonary chondroma and 33 cases of pulmonary hamartoma. SDHB expression was retained in all 33 pulmonary hamartomas, and lost in the majority of evaluable chondromas (five of six). Of the five patients with chondromas showing SDHB loss, four had definitive Carney triad. Most patients with pulmonary hamartomas were older males with small solitary masses, whereas chondromas often presented as multiple masses in young females. CONCLUSION: Loss of SDHB immunohistochemical expression can be useful for differentiating pulmonary chondromas from hamartomas, and potentially identifying patients with Carney triad.
Assuntos
Condroma/classificação , Hamartoma/classificação , Leiomiossarcoma/classificação , Neoplasias Pulmonares/classificação , Paraganglioma Extrassuprarrenal/classificação , Neoplasias Gástricas/classificação , Succinato Desidrogenase/metabolismo , Condroma/patologia , Feminino , Hamartoma/patologia , Humanos , Imuno-Histoquímica , Leiomiossarcoma/patologia , Neoplasias Pulmonares/patologia , Masculino , Paraganglioma Extrassuprarrenal/patologia , Neoplasias Gástricas/patologiaRESUMO
A distinct subset of thoracic sarcomas with undifferentiated rhabdoid morphology and SMARCA4 inactivation has recently been described, and potential targeted therapy for SMARC-deficient tumors is emerging. We sought to validate the clinicopathological features of SMARCA4-deficient thoracic sarcomas. Clinicopathological information was gathered for 40 undifferentiated thoracic tumors with rhabdoid morphology (mediastinum (n=18), lung (n=14), pleura (n=8)). Thymic carcinomas (n=11) were used as a comparison group. Immunohistochemistry included BRG1 (SMARCA4), BRM (SMARCA2), INI-1 (SMARCB1), pan-cytokeratin, desmin, NUT, S-100 protein, TTF1, CD34, and SOX2. BRG1 loss was present in 12 of 40 rhabdoid thoracic tumors (30%): 7 of 18 in mediastinum (39%), 2 of 8 in pleura (25%), and 3 of 14 in lung (21%). All BRG1-deficient tumors tested for BRM (n=8) showed concomitant loss. All thymic carcinomas showed retained BRG1 and INI-1. Morphologically, tumors with BRG1 loss showed sheets of monotonous ovoid cells with indistinct cell borders, abundant eosinophilic cytoplasm, and prominent nucleoli. Scattered areas with rhabdoid morphology (ie, eccentric nuclei, dense eosinophilic cytoplasm, discohesion) were present in all the cases. SMARCA4/BRG1-deficient sarcomas showed rare cells positive for cytokeratin in 10 cases (83%). One showed rare TTF1-positive cells. All were negative for desmin, NUT, and S-100 protein. CD34 was positive in three of five (60%) BRG1-deficient tumors tested. SOX2 was positive in all four BRG1-deficient tumors tested, and negative in all seven tested cases with retained BRG1. SMARCA4/BRG1-deficient sarcomas occurred at median age of 59 years (range 44-76) with male predominance (9:3) and had worse 2-year survival compared with BRG1-retained tumors (12.5% vs 64.4%, P=0.02). SMARCA4-deficient thoracic sarcomas can be identified based on their distinctive high-grade rhabdoid morphology, and the diagnosis can be confirmed by immunohistochemistry. Identification of these tumors is clinically relevant due to their aggressive behavior, poor prognosis, and potential targeted therapy.
Assuntos
DNA Helicases/genética , Proteínas Nucleares/genética , Sarcoma/genética , Sarcoma/patologia , Neoplasias Torácicas/genética , Neoplasias Torácicas/patologia , Fatores de Transcrição/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , DNA Helicases/análise , DNA Helicases/biossíntese , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/análise , Proteínas Nucleares/biossíntese , Sarcoma/diagnóstico , Neoplasias Torácicas/diagnóstico , Fatores de Transcrição/análise , Fatores de Transcrição/biossíntese , Adulto JovemRESUMO
Hemosiderotic fibrolipomatous tumor is an unusual, distinctive soft tissue neoplasm with locally recurring potential, which most commonly occurs in the ankle and foot. Morphologic evidence strongly suggests that hemosiderotic fibrolipomatous tumor is related to another rare, locally aggressive tumor of the distal extremities, pleomorphic hyalinizing angiectatic tumor, with areas identical to hemosiderotic fibrolipomatous tumor seen at the periphery in most if not all pleomorphic hyalinizing angiectatic tumor. This morphologic evidence is further supported by molecular genetic data, showing recurrent TGFBR3 and/or MGEA5 rearrangements in both hemosiderotic fibrolipomatous tumor and pleomorphic hyalinizing angiectatic tumor. A possible link between hemosiderotic fibrolipomatous tumor and yet another low-grade sarcoma of the distal extremities, myxoinflammatory fibroblastic sarcoma, has also been suggested based on the occurrence of unusual examples of hemosiderotic fibrolipomatous tumor showing progression to myxoid sarcoma, demonstrating some but not all features of myxoinflammatory fibroblastic sarcoma. These "hybrid hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcoma" also commonly show TGFBR3 and/or MGEA5 rearrangements. However, classic myxoinflammatory fibroblastic sarcoma lacks areas resembling hemosiderotic fibrolipomatous tumor, and shows a very low frequency of TGFBR3 and/or MGEA5 rearrangements in prospectively diagnosed cases. This suggests that so-called "hybrid hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcoma" represents a form of malignant progression within hemosiderotic fibrolipomatous tumor, rather than a lesion strictly related to classic myxoinflammatory fibroblastic sarcoma. This article will review the morphologic features, genetic features, and differential diagnosis of these rare neoplasms, and discuss their interrelation, or lack thereof.
Assuntos
Biomarcadores Tumorais/genética , Fibrossarcoma/patologia , Lipoma/patologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Diagnóstico Diferencial , Humanos , Lipoma/diagnóstico , Sarcoma/diagnóstico , Neoplasias de Tecidos Moles/diagnósticoRESUMO
Several targetable genetic alterations have been found in lung cancer, predominantly in adenocarcinomas, which have led to important therapeutic advancements with the advent of targeted therapy. In contrast, the molecular features and presence of targetable genetic abnormalities in pulmonary sarcomatoid carcinomas are largely unknown. Thirty-three cases of pulmonary sarcomatoid carcinoma were tested for approximately 2800 mutations in 50 oncogenes and tumor-suppressor genes, including EGFR, KRAS, NRAS, TP53, BRAF, ERBB2, JAK3, AKT1, ATM, MET, KIT, and PIK3CA. ALK immunostaining was performed, and ALK FISH was performed on cases with any degree of staining. Twenty-four of the 33 cases (72%) had at least one genetic abnormality: 19 cases (58%) had TP53 mutations; 10 cases (30%) had KRAS mutations; AKT1, JAK3, BRAF, NRAS, and PIK3CA mutations were observed in 1 case each (3%). Six of the 19 cases (32%) with a mutation in TP53 had simultaneous mutations in KRAS (18%). The cases with alterations in JAK3, BRAF, and NRAS also had mutations in TP53. The case showing a mutation in PIK3CA had a mutation in KRAS. No EGFR mutations were observed. One case had ALK gene rearrangement. ALK rearrangement was observed in a single case of sarcomatoid carcinoma (3%), which has currently available targeted therapy. Four tumors had mutations in genes with experimental molecular-based therapy, including BRAF, NRAS, PIK3CA, and AKT1. Testing for targetable mutations should be considered for patients with pulmonary sarcomatoid carcinoma, as a subset may benefit from currently approved drugs or clinical trials of novel therapeutic options available for other types of lung cancer.
Assuntos
Biomarcadores Tumorais/genética , Carcinossarcoma/genética , Neoplasias Pulmonares/genética , Mutação , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Carcinossarcoma/tratamento farmacológico , Carcinossarcoma/enzimologia , Carcinossarcoma/patologia , Análise Mutacional de DNA , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Fenótipo , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
Solitary fibrous tumor is a mesenchymal neoplasm exhibiting a broad spectrum of biological behavior and harboring the NAB2-STAT6 fusion. Clinicopathologic parameters are currently used in risk-prediction models for solitary fibrous tumor, but the molecular determinants of malignancy in solitary fibrous tumors remain unknown. We proposed that the activation of telomere maintenance pathways confers a perpetual malignant phenotype to these tumors. Therefore, we investigated telomerase reverse transcriptase (TERT) reactivation induced by promoter mutations as a potential molecular mechanism for aggressive clinical behavior in solitary fibrous tumor. The retrospective study included tumor samples from 94 patients with solitary fibrous tumor (31 thoracic and 63 extra-thoracic). Follow-up information was available for 68 patients (median, 46 months). TERT promoter mutation analysis was performed by PCR and Sanger sequencing, and TERT mRNA expression was assessed by real-time quantitative reverse transcription PCR. Patients were stratified into clinicopathologic subgroups (high-risk (n=20), moderate-risk (n=28), and low-risk (n=46)) according to the risk-stratification model proposed by Demicco et al. TERT promoter mutations were identified in 26 of 94 (28%) solitary fibrous tumors: -124C>T in 23 tumors (88%), -124C>A in 1 tumor (4%), and -146C>T in 2 tumors (8%). Real-time quantitative reverse transcription PCR revealed that TERT mRNA expression was higher in all solitary fibrous tumors with the mutant TERT promoter than those with the wild-type TERT promoter. TERT promoter mutations were strongly associated with high-risk clinicopathologic characteristics and outcome. An adverse event (relapse, death) occurred in 16 of 68 (24%) patients, 12 with solitary fibrous tumors with TERT promoter mutations and 4 with the wild-type TERT promoter. TERT promoter mutations were strongly associated with older age (P=0.006), larger tumor size (P=0.000002), higher risk classifications (P=2.9 × 10-9), and a worse event-free survival (P=0.0082). Thus, TERT promoter mutations in solitary fibrous tumor influence gene expression and are associated with adverse patient outcome. Integrating TERT promoter mutational status with existing multivariable risk-prediction models might improve risk prediction in patients with solitary fibrous tumor.
Assuntos
Regiões Promotoras Genéticas/genética , Tumores Fibrosos Solitários/genética , Telomerase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Tumores Fibrosos Solitários/mortalidade , Tumores Fibrosos Solitários/patologia , Adulto JovemRESUMO
Granulomas are frequently encountered by pathologists in all types of lung specimens and arise from diverse etiologies. They should always be reported as necrotizing or non-necrotizing, with microorganism stains performed to evaluate for infection. With attention to distribution, quality (poorly vs well-formed), associated features, and correlation with clinical, radiologic, and laboratory data, the differential diagnosis for granulomatous lung disease can usually be narrowed to a clinically helpful "short list." This review describes a practical approach to pulmonary granulomas and reviews the clinicopathological aspects of common entities, including infectious (mycobacteria, fungi) and noninfectious (hypersensitivity pneumonitis, sarcoid, and vasculitis) causes.
Assuntos
Pneumopatias , Humanos , Diagnóstico Diferencial , Pneumopatias/patologia , Pneumopatias/diagnóstico , Granuloma do Sistema Respiratório/patologia , Granuloma do Sistema Respiratório/diagnóstico , Granuloma/patologia , Granuloma/diagnóstico , Pulmão/patologia , Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/patologia , Sarcoidose Pulmonar/patologia , Sarcoidose Pulmonar/diagnóstico , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/patologiaRESUMO
CASE PRESENTATION: A 62-year-old woman came to our hospital with worsening cough and dyspnea over the preceding week, during which time she had been treated with azithromycin and prednisone for suspected pneumonia. She had no fever, chills, or sweats, but her cough had become productive of clear to blood-tinged phlegm during the interval. Medical history was significant for insulin-dependent diabetes mellitus and OSA. She had quit smoking 44 years earlier and had no history of lung disease. She was a bank teller residing in southeastern Minnesota and described no relevant inhalational or environmental exposures, drug use, aspiration, or travels preceding her illness.
Assuntos
Tosse , Dispneia , Tomografia Computadorizada por Raios X , Humanos , Feminino , Pessoa de Meia-Idade , Tosse/etiologia , Tosse/diagnóstico , Dispneia/etiologia , Dispneia/diagnóstico , Diagnóstico Diferencial , Nódulos Pulmonares Múltiplos/diagnóstico , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/etiologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/complicaçõesRESUMO
CONTEXT.: Primary thoracic neoplasms are rare in children, whereas nonneoplastic mass lesions or cysts and metastases are more common, and there is a relative paucity of comprehensive histopathologic and molecular data. OBJECTIVE.: To define the clinicopathologic spectrum of neoplastic and nonneoplastic diseases observed in resected mass lesions in the chest of pediatric patients, and to identify somatic alterations observed in primary neoplasms. DESIGN.: Clinicopathologic features of thoracic mass lesions (n = 385) resected from 373 patients aged ≤21 years in a 25-year period (1993-2018) were included. Primary neoplasms having sufficient material were tested by a laboratory-developed comprehensive genomic profiling assay that assesses tumor mutational burden, microsatellite instability, somatic sequence variants, gene amplifications, fusions, and specific transcript variants. RESULTS.: The most commonly resected space-occupying lesions were nonneoplastic mass lesions and cysts or malformations, resected in 117 (31.4%) and 58 of 373 patients (15.5%) respectively. Metastatic neoplasms were observed in 169 of 373 patients (45.3%; mean age 14.4 years, range 1-21 years); the most common was osteosarcoma (68 of 169; 40.2% of metastases). Primary lung neoplasms occurred in 24 of 373 patients (6.4%; mean age 14.5 years, range 6 months-21 years), and 16 patients had primary extrapulmonary thoracic tumors. Carcinoid tumor was the most common primary lung neoplasm (7 typical, 3 atypical). Molecular testing showed a prevalence of somatic pathogenic or likely pathogenic mutations and copy-number alterations. No fusions or splice variants were identified. Tumors were microsatellite-stable with low tumor mutational burden. CONCLUSIONS.: Resected pediatric thoracic mass lesions are more likely to be metastatic lesions, congenital cysts or malformations, or nonneoplastic lesions compared to primary thoracic neoplasms, which are encountered at a low frequency and tend to have relatively simple genetic profiles.
RESUMO
Primary pulmonary myxoid sarcoma (PPMS) and thoracic angiomatoid fibrous histiocytoma (AFH) are rare neoplasms with EWSR1 fusions and overlapping morphology. Both tumor types often show epithelial membrane antigen expression, but AFH characteristically co-expresses desmin. We encountered a case of PPMS with the unexpected finding of patchy, strong anaplastic lymphoma kinase (ALK) (previously reported in AFH) and synaptophysin expression. We evaluated a cohort of PPMS and thoracic AFH with systematic morphologic comparison and surveyed for aberrant expression of ALK and synaptophysin. Medical records and slides were reviewed for 16 molecularly confirmed cases of PPMS (n=5) and thoracic AFH (n=11). Each case was scored for morphologic characteristics typical of PPMS and/or AFH. ALK, synaptophysin, chromogranin, desmin, and epithelial membrane antigen immunostains were performed on cases with available tissue. AFH and PPMS cases showed similar age at presentation and long-term tumor behavior. Almost all cases of PPMS and AFH had a fibrous pseudocapsule and lymphoid rim. All PPMS had myxoid stroma and reticular growth pattern, but these features were also present in a subset of AFH. Synaptophysin expression was present in 6 of 11 AFH and 1 of 5 PPMS; all tested cases were negative for chromogranin (n=15). One case of AFH and 1 case of PPMS showed focally strong coexpression of synaptophysin and ALK. AFH and PPMS show considerable clinicopathologic overlap. When supportive, the immunohistochemical findings described may aid in diagnosis before molecular confirmation. PPMS and AFH may be morphologic variants of the same clinicopathologic entity, which can show more immunophenotypic variability than previously reported.
Assuntos
Histiocitoma Fibroso Benigno , Histiocitoma Fibroso Maligno , Humanos , Sinaptofisina , Mucina-1 , Desmina , Cromograninas , Histiocitoma Fibroso Maligno/genética , Histiocitoma Fibroso Maligno/cirurgia , Histiocitoma Fibroso Maligno/diagnóstico , Receptores Proteína Tirosina QuinasesRESUMO
Gangliocytic paragangliomas are rare neoplasms occurring almost exclusively in the ampullary region of the gastrointestinal tract. Although these tumors are not typically considered in the differential diagnosis of primary pulmonary neoplasia, 5 cases of primary pulmonary gangliocytic paragangliomas have been previously reported. Herein we report our experience with 3 additional examples, all referred to our Anatomic Pathology Consultation service. The patients (a 32-year-old man, a 69-year-old woman and a 55-year-old man) each presented with an endobronchial (2 cases) or upper lobe lung mass, ranging from 1.5 to 2.5 cm in maximum dimension. Biopsy and endobronchial debulking specimens demonstrated the classic triphasic morphology of gangliocytic paraganglioma, with epithelial, spindled and ganglion-like cells. By immunohistochemistry, the tumors were positive for keratin, synaptophysin and chromogranin A in the epithelial component, S100 protein and glial fibrillary acidic protein (GFAP) in the Schwannian spindled cells, and synaptophysin in ganglion cells. TTF1 expression was seen in the epithelial components of 2 cases. The Ki-67 labelling index was low (<2%). Primary pulmonary gangliocytic paragangliomas should be distinguished from carcinoid tumors, given the different natural histories and risk stratification approaches for these morphologically similar tumors. Awareness that gangliocytic paraganglioma may occur in the lung and appropriate immunohistochemical studies are key to correct diagnosis.
Assuntos
Biomarcadores Tumorais , Tumor Carcinoide , Imuno-Histoquímica , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Diagnóstico Diferencial , Biomarcadores Tumorais/análise , Adulto , Tumor Carcinoide/patologia , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/química , Paraganglioma/patologia , Paraganglioma/diagnóstico , Biópsia , Valor Preditivo dos TestesRESUMO
Prognostic stratification of pulmonary carcinoids into "typical" and "atypical" categories requires examination of large tissue volume. However, there is a need for tools that provide similar prognostic information on small biopsy samples. Ki-67 and OTP immunohistochemistry have shown promising prognostic value in studies of resected pulmonary carcinoids, but prognostic value when using biopsy/cytology specimens is unclear. Ki-67 immunohistochemistry was performed on small biopsy/cytology specimens from pulmonary carcinoid tumors (n=139), and labeling index was scored via automated image analysis of at least 500 cells. OTP immunohistochemistry was performed on 70 cases with sufficient tissue and scored as positive or negative (<20% tumor nuclei staining). Higher Ki-67 index was associated with worse disease-specific progression-free survival (ds-PFS), with 3% and 4% thresholds having similarly strong associations with ds-PFS ( P <0.001, hazard ratio ≥11). Three-year ds-PFS was 98% for patients with Ki-67 <3% and 89% for patients with Ki-67≥3% ( P =0.0006). The optimal Ki-67 threshold for prediction of typical versus atypical carcinoid histology on subsequent resection was 3.21 (AUC 0.68). Negative OTP staining approached significance with atypical carcinoid histology ( P =0.06) but not with ds-PFS ( P =0.24, hazard ratio=3.45), although sample size was limited. We propose that Ki-67 immunohistochemistry may contribute to risk stratification for carcinoid tumor patients based on small biopsy samples. Identification of a 3% hot-spot Ki-67 threshold as optimal for prediction of ds-PFS is notable as a 3% Ki-67 threshold is currently used for gastrointestinal neuroendocrine tumor stratification, allowing consideration of a unified classification system across organ systems.
Assuntos
Biomarcadores Tumorais , Tumor Carcinoide , Antígeno Ki-67 , Neoplasias Pulmonares , Intervalo Livre de Progressão , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Biomarcadores Tumorais/análise , Biópsia , Tumor Carcinoide/patologia , Tumor Carcinoide/mortalidade , Tumor Carcinoide/química , Tumor Carcinoide/cirurgia , Imuno-Histoquímica , Antígeno Ki-67/análise , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/química , Neoplasias Pulmonares/cirurgia , Valor Preditivo dos Testes , Fatores de TempoAssuntos
Bursite/diagnóstico , Articulação do Cotovelo , Olécrano , Prototheca/isolamento & purificação , Dermatopatias Infecciosas/diagnóstico , Antifúngicos/uso terapêutico , Bursite/tratamento farmacológico , Bursite/cirurgia , Técnicas Citológicas , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Prototheca/efeitos dos fármacos , Dermatopatias Infecciosas/tratamento farmacológico , Dermatopatias Infecciosas/cirurgia , Resultado do TratamentoRESUMO
Rearrangements of the EWSR1 gene are found in an increasing number of human neoplasms, including several tumors that can involve the skin: Ewing sarcoma/primitive neuroectodermal tumor, angiomatoid (malignant) fibrous histiocytoma, myoepithelioma of soft tissue, and clear cell sarcoma. Although these tumors share this common genetic link, they have very different clinical features, morphology, immunophenotype, and sometimes fusion gene partners; these will be the subjects of this review.
Assuntos
Proteínas de Ligação a Calmodulina/genética , Fusão Gênica , Rearranjo Gênico , Proteínas de Fusão Oncogênica/genética , Proteínas de Ligação a RNA/genética , Neoplasias Cutâneas/genética , Proteínas de Ligação a Calmodulina/metabolismo , Regulação Neoplásica da Expressão Gênica , Histiocitoma Fibroso Maligno/genética , Histiocitoma Fibroso Maligno/metabolismo , Histiocitoma Fibroso Maligno/patologia , Humanos , Hibridização in Situ Fluorescente , Mioepitelioma/genética , Mioepitelioma/metabolismo , Mioepitelioma/patologia , Tumores Neuroectodérmicos Primitivos/genética , Tumores Neuroectodérmicos Primitivos/metabolismo , Tumores Neuroectodérmicos Primitivos/patologia , Proteínas de Fusão Oncogênica/metabolismo , Proteína EWS de Ligação a RNA , Proteínas de Ligação a RNA/metabolismo , Sarcoma de Células Claras/genética , Sarcoma de Células Claras/metabolismo , Sarcoma de Células Claras/patologia , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologiaRESUMO
CONTEXT.: Nuclear protein in testis (NUT) carcinoma is an aggressive carcinoma defined by NUTM1 gene rearrangement. Diagnostic challenges include morphologic overlap with poorly differentiated squamous cell carcinoma, small cell carcinoma, thoracic SMARCA4-deficient undifferentiated tumor, and other small round blue cell tumors. OBJECTIVE.: To comprehensively study the immunohistochemistry (IHC) features of a large cohort of NUT carcinomas. DESIGN.: Fifty-seven NUT carcinoma cases were identified from 2012-2022, including 38 thoracic/mediastinal, 13 head and neck/sinonasal, and 6 from other sites. Pathology reports and available slides were reviewed. Comprehensive IHC studies were performed on available cases. RESULTS.: Keratin stains showed variable positivity and were entirely negative in 15% (8 of 55) of cases. p40 was only positive in 65% (24 of 37) of cases, implying inferior sensitivity when compared to p63 (87% sensitivity, 20 of 23 cases) and other squamous cell markers. Neuroendocrine markers were focally/weakly positive in few cases; however, INSM1 was positive in 54% (7 of 13) of cases, indicating a possible diagnostic pitfall. TTF-1 was mostly negative with focal positivity in 26% (10 of 38) of cases. Occasional CD34 (15%, 3 of 20 cases) and CD99 (21%, 3 of 14 cases) positivity could also cause potential diagnostic confusion. S100, desmin, CD45, and SALL4 were rarely positive. BRG1 and INI1 were retained in all cases. Ki-67 proliferative index was high (median, 60%). PD-L1 was negative in all tested cases. CONCLUSIONS.: This comprehensive IHC study demonstrates the immunohistochemical spectrum of NUT carcinoma. The findings can help narrow the differential diagnosis and recognize potential pitfalls.
RESUMO
OBJECTIVES: Bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT) and sclerosing pneumocytoma (SP) are both rare and morphologically unique peripheral lung tumors with indolent behavior. These tumors have not been previously described as showing overlapping morphologic features and are generally genetically distinct. METHODS: Two cases were recently encountered that show hybrid morphologic features between BA/CMPT and SP, and the morphology and immunophenotype are described in detail. RESULTS: Both cases showed interstitial round cells typical of SP (TTF1+, EMA+), as well as areas more typical of BA/CMPT. One case showed BRAFV600E expression in the BA/CMPT areas but not in the SP-like cells. CONCLUSIONS: Although it is possible that these cases represent collision tumors or are examples of unusual metaplastic epithelial changes in SP, they also raise the possibility that these 2 entities could occasionally coexist in true hybrid tumors.