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1.
Am J Surg Pathol ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38919071

RESUMO

Wolffian tumor and its nosologic relative, the recently defined STK11 adnexal tumor are rare neoplasms thought to arise from mesonephric remnants. These tumors typically arise in the broad ligament, fallopian tube, and ovarian hilum and although most are associated with a good prognosis, up to 50% of STK11 adnexal tumors demonstrate aggressive clinical behavior. The chief differential diagnoses include endometrioid adenocarcinoma and sex cord stromal tumors. However, the morphologic and immunohistochemical features of these tumors exhibit considerable overlap with peritoneal mesothelioma. To fully characterize their immunophenotypic signature, we examined a total of 21 cases (18 Wolffian and 3 STK11 adnexal tumors) with standard markers used in the diagnosis of mesothelioma. Morphologic and immunohistochemical (IHC) features were reviewed and additional IHC performed for cases with available material. Patient age ranged from 25 to 73 (mean: 51) years. Sites included adnexa/broad ligament (6, 28%), paratubal (5, 24%), ovary/paraovarian (5, 24%), tubal (intraluminal) (2, 9.5%), pelvis (2, 9.5%), and liver (1, 5%). The mean tumor size was 9.3 cm (range: 0.2 to 22 cm). The histomorphology in most cases (14/21, 66%) consisted of tubular to solid sheets of neoplastic cells lined by columnar to cuboidal cells containing uniform round to oval nuclei. Compressed tubules with slit-like lumens and sieve-like pattern were also seen in at least 7 (33%) cases. Three cases demonstrated interanastomosing cords and trabeculae of epithelioid cells with cribriform and microacinar patterns growing within prominent myxoid stroma as described in STK11 adnexal tumors. In the cases with available IHC for 3 mesothelial markers (calretinin, WT1, D2-40), 55.5% (5 of 9) showed reactivity with all 3 markers. In cases with at least 2 available mesothelial markers, 69% (11/16) were positive for 2 markers (mostly calretinin and WT1). Claudin-4, MOC31, and BER-EP4 were negative in most cases tested (78% [7/9], 71.4% [5/7], and 100% [6/6], respectively). Given the resemblance to mesothelioma, there was initial strong consideration and/or actual misdiagnosis of mesothelioma in 3 cases (14%). In summary, the morphologic and immunohistochemical features of Wolffian tumor and its recently defined relative, STK11 adnexal tumor, can lead to misdiagnosis of mesothelioma, particularly when encountered in the disseminated or metastatic setting. Wolffian tumor and STK11 adnexal tumor should be considered in the differential diagnosis of all pelvic and peritoneal mesotheliomas.

2.
Lancet Rheumatol ; 6(5): e314-e327, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574742

RESUMO

Proteinase 3 (PR3)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is one of two major ANCA-associated vasculitis variants and is pathogenically linked to granulomatosis with polyangiitis (GPA). GPA is characterised by necrotising granulomatous inflammation that preferentially affects the respiratory tract. The small vessel vasculitis features of GPA are shared with microscopic polyangiitis. Necrotising granulomatous inflammation of GPA can lead to PR3-ANCA and small vessel vasculitis via activation of neutrophils and monocytes. B cells are central to the pathogenesis of PR3-ANCA-associated vasculitis. They are targeted successfully by remission induction and maintenance therapy with rituximab. Relapses of PR3-ANCA-associated vasculitis and toxicities associated with current standard therapy contribute substantially to remaining mortality and damage-associated morbidity. More effective and less toxic treatments are sought to address this unmet need. Advances with cellular and novel antigen-specific immunotherapies hold promise for application in autoimmune disease, including PR3-ANCA-associated vasculitis. This Series paper describes the inter-related histopathological and clinical features, pathophysiology, as well as current and future targeted treatments for PR3-ANCA-associated vasculitis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Humanos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/terapia , Mieloblastina/imunologia , Rituximab/uso terapêutico
3.
Semin Respir Crit Care Med ; 45(3): 287-304, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38631369

RESUMO

Interstitial lung disorders are a group of respiratory diseases characterized by interstitial compartment infiltration, varying degrees of infiltration, and fibrosis, with or without small airway involvement. Although some are idiopathic (e.g., idiopathic pulmonary fibrosis, idiopathic interstitial pneumonias, and sarcoidosis), the great majority have an underlying etiology, such as systemic autoimmune rheumatic disease (SARD, also called Connective Tissue Diseases or CTD), inhalational exposure to organic matter, medications, and rarely, genetic disorders. This review focuses on diagnostic approaches in interstitial lung diseases associated with SARDs. To make an accurate diagnosis, a multidisciplinary, personalized approach is required, with input from various specialties, including pulmonary, rheumatology, radiology, and pathology, to reach a consensus. In a minority of patients, a definitive diagnosis cannot be established. Their clinical presentations and prognosis can be variable even within subsets of SARDs.


Assuntos
Doenças do Tecido Conjuntivo , Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/complicações , Prognóstico , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/complicações , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/complicações
4.
Arch Pathol Lab Med ; 148(4): 419-429, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37594899

RESUMO

CONTEXT.­: The pathologic diagnosis of pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is challenging. OBJECTIVE.­: To evaluate the diagnostic usefulness and limitations of current diagnostic strategies for pulmonary MALT lymphoma. DESIGN.­: A retrospective review of 120 cases of pulmonary MALT lymphoma from 2014 through 2021 was performed. RESULTS.­: Clinicoradiologic presentations overlapped with previous observations in patients with MALT lymphoma, such as a wide age range, female predominance, frequent association with autoimmune disease or immunodeficiency, and broad imaging findings. The histopathologic diagnosis was based on a combination of morphology, immunohistochemistry, and demonstration of B-cell lineage clonality. Two-thirds (76 of 113) of MALT lymphomas had lymphoplasmacytoid cytomorphology. Occasionally, MALT lymphomas were associated with granulomas/giant cells (29%, 35 of 120) or immunoglobulin deposition disease (21%, 25 of 120), including light chain/heavy chain deposition disease, amyloidosis, and/or crystal storing histiocytosis. While CD5, CD10, Bcl-2, and Bcl-6 rarely revealed aberrancies, aberrant CD43 expression either on B-cells or on plasma cells was detected in 42% (27 of 64) of cases, including cases for which proof of clonality could not be obtained. κ/λ in situ hybridization was particularly useful for tumors with lymphoplasmacytoid morphology but performed poorly in lymphomas having no plasmacytic differentiation. κ/λ immunohistochemistry showed no additional usefulness when applied together with κ/λ in situ hybridization. Immunoglobulin gene rearrangement studies by polymerase chain reaction achieved high detection rates of clonality in all cytomorphologic subgroups. CONCLUSIONS.­: Our study offers a practical evaluation of common diagnostic tests in pulmonary MALT lymphoma. We offer recommendations for a diagnostic workup that takes into consideration the usefulness and the specific limitations of the various diagnostic strategies.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Humanos , Feminino , Masculino , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/genética , Linfócitos B/patologia , Plasmócitos/patologia , Rearranjo Gênico , Imuno-Histoquímica
5.
Mod Pathol ; 36(9): 100221, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37236510

RESUMO

Transbronchial cryobiopsy (TBCB) is increasingly used for the diagnosis of fibrosing interstitial pneumonias, but there are few detailed descriptions of the pathologic findings in such cases. It has been proposed that a combination of patchy fibrosis and fibroblast foci with an absence of alternative features is diagnostic of usual interstitial pneumonia (UIP; ie, idiopathic pulmonary fibrosis [IPF]) in TBCB. In this study, we reviewed 121 TBCB in which a diagnosis of fibrotic hypersensitivity pneumonitis (FHP; n = 83) or IPF (n = 38) was made by multidisciplinary discussion and evaluated a range of pathologic features. Patchy fibrosis was found in 65 of 83 (78%) biopsies from FHP and 32of 38 (84%) biopsies from UIP/IPF cases. Fibroblast foci were present in 47 of 83 (57%) FHP and 27 of 38 (71%) UIP/IPF cases. Fibroblast foci/patchy fibrosis combined did not favor either diagnosis. Architectural distortion was seen in 54 of 83 (65%) FHP and 32 of 38 (84%) UIP/IPF cases (odds ratio [OR] for FHP, 0.35; P = .036) and honeycombing in 18 of 83 (22%) and 17 of 38 (45%), respectively (OR, 0.37; P = .014). Airspace giant cells/granulomas were present in 13 of 83 (20%) FHP and 1 of 38 (2.6%) UIP/IPF cases (OR for FHP, 6.87; P = .068), and interstitial giant cells/granulomas in 20 of 83 (24%) FHP and 0 of 38 (0%) UIP/IPF (OR, 6.7 x 106; P = .000). We conclude that patchy fibrosis plus fibroblast foci can be found in TBCB from both FHP and UIP/IPF. The complete absence of architectural distortion/honeycombing favors a diagnosis of FHP, as does the presence of airspace or interstitial giant cells/granulomas, but these measures are insensitive, and many cases of FHP cannot be separated from UIP/IPF on TBCB.


Assuntos
Alveolite Alérgica Extrínseca , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/patologia , Doenças Pulmonares Intersticiais/patologia , Fibrose , Biópsia , Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/patologia , Granuloma/patologia , Pulmão/patologia
7.
Am J Surg Pathol ; 47(3): 281-295, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36597787

RESUMO

The use of lymphoid interstitial pneumonia (LIP) as a diagnostic term has changed considerably since its introduction. Utilizing a multi-institutional collection of 201 cases from the last 20 years that demonstrate features associated with the LIP rubric, we compared cases meeting strict histologic criteria of LIP per American Thoracic Society (ATS)/European Respiratory Society (ERS) consensus ("pathologic LIP"; n=62) with cystic cases fulfilling radiologic ATS/ERS criteria ("radiologic LIP"; n=33) and with other diffuse benign lymphoid proliferations. "Pathologic LIP" was associated with immune dysregulation including autoimmune disorders and immune deficiency, whereas "radiologic LIP" was only seen with autoimmune disorders. No case of idiopathic LIP was found. On histology, "pathologic LIP" represented a subgroup of 70% (62/88) of cases with the distinctive pattern of diffuse expansile lymphoid infiltrates. In contrast, "radiologic LIP" demonstrated a broad spectrum of inflammatory patterns, airway-centered inflammation being most common (52%; 17/33). Only 5 cases with radiologic cysts also met consensus ATS/ERS criteria for "pathologic LIP." Overall, broad overlap was observed with the remaining study cases that failed to meet consensus criteria for "radiologic LIP" and/or "pathologic LIP." These data raise concerns about the practical use of the term LIP as currently defined. What radiologists and pathologist encounter as LIP differs remarkably, but neither "radiologic LIP" nor "pathologic LIP" present with sufficiently distinct findings to delineate such cases from other patterns of diffuse benign lymphoid proliferations. As a result of this study, we believe LIP should be abandoned as a pathologic and radiologic diagnosis.


Assuntos
Pneumonias Intersticiais Idiopáticas , Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/patologia , Pulmão/patologia , Pneumonias Intersticiais Idiopáticas/diagnóstico , Pneumonias Intersticiais Idiopáticas/patologia , Radiografia
8.
Arch Pathol Lab Med ; 147(5): 525-533, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35917487

RESUMO

CONTEXT.­: Diffuse parenchymal lung disease (DPLD) is a well-recognized complication of systemic connective tissue disease (CTD) but rarely arises in patients with psoriasis or psoriatic arthritis, a poorly understood phenomenon. OBJECTIVE.­: To characterize DPLD associated with psoriasis or psoriatic arthritis, with or without prior immunomodulation. DESIGN.­: Pathology consultation files were searched for patients having psoriasis or psoriatic arthritis and DPLD. After excluding cases with active infection or smoking-related DPLD only, 44 patients (22 women; median age, 60 years; range, 23-81 years) were enrolled. Clinical history and pathology slides were reviewed. RESULTS.­: Twenty-seven of 44 patients (61%) had psoriatic arthritis; the remainder had psoriasis alone. Most presented many years later with nonspecific respiratory symptoms. Nearly one-third had no prior immunosuppression, and most had no concomitant CTD. Radiographically, ground-glass opacities, consolidation, and/or reticulation were typical. Histologically, nonspecific interstitial pneumonia and unclassifiable fibrosis were seen in 24 patients (55%) and 8 patients (18%), respectively; usual interstitial pneumonia and airway-centered fibrosis were rare. Superimposed acute lung injury was common, usually manifesting as organizing pneumonia. Lymphoplasmacytic infiltrates, lymphoid aggregates, and chronic pleuritis were frequent. Interstitial granulomas were seen in 17 patients (39%) but were usually rare, poorly formed, and nonnecrotizing. No histologic differences were apparent among patients with or without concomitant CTDs or prior therapy. CONCLUSIONS.­: Some patients with psoriasis or psoriatic arthritis develop clinically significant DPLD, even without prior therapy. Histopathologic findings mirror changes seen with other CTDs. Additional studies are warranted to clarify the association between psoriasis or psoriatic arthritis and DPLD.


Assuntos
Artrite Psoriásica , Doenças Pulmonares Intersticiais , Patologia Cirúrgica , Psoríase , Humanos , Feminino , Pessoa de Meia-Idade , Artrite Psoriásica/complicações , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/diagnóstico , Psoríase/complicações , Fibrose
9.
Children (Basel) ; 9(7)2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35883926

RESUMO

Intracardiac masses are unusual findings in infants, and most of them are benign. Nevertheless, they may be associated with a significant degree of hemodynamic instability and/or arrhythmias. Malignant tumors of the heart rarely occur in children. Rhabdoid tumors are aggressive tumors with a dismal prognosis even when diagnosed early. Although rhabdomyomas are common cardiac tumors in infants, they are mostly benign. The most common sites of involvement are the kidneys and central nervous system, but soft tissues, lungs, and ovaries may also be affected. The diagnosis can be challenging, particularly in sites where they do not usually occur. In the present paper, we report the case of a 2-year-old boy diagnosed with cardiac rhabdoid tumor highlighting the importance of molecular studies and recent genetic discoveries with the purpose of improving the management of such cases. The aim of this educational case report and literature review is to raise awareness of cardiac masses in children and to point out diagnostic hints toward a cardiac tumor on various imaging modalities. Given the rarity of all tumors involving the heart and the lack of symptom specificity, a high degree of suspicion is needed to arrive at the correct diagnosis.

10.
Arch Pathol Lab Med ; 146(7): 791-804, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35319744

RESUMO

CONTEXT.­: Studies of lungs in patients with COVID-19 have focused on early findings. OBJECTIVE.­: To systematically study histopathologic and imaging features and presence of SARS-CoV-2 RNA in lung tissue from patients in later stages of COVID-19. DESIGN.­: Autopsies, explants, surgical lung biopsies, transbronchial biopsies, cryobiopsies, and needle biopsies from patients with COVID-19 whose onset of symptoms/confirmed diagnosis was more than 28 days before the procedure were studied. Available images were reviewed. Reverse transcription droplet digital polymerase chain reaction for SARS-CoV-2 RNA was performed on lung tissue. RESULTS.­: Of 44 specimens (43 patients; median age, 59.3 years; 26 [60.5%] male) features of acute lung injury (ALI) were seen in 39 (88.6%), predominantly organizing pneumonia and diffuse alveolar damage, up to 298 days after onset of COVID-19. Fibrotic changes were found in 33 specimens (75%), most commonly fibrotic diffuse alveolar damage (n = 22) and cicatricial organizing pneumonia (n = 12). Time between acquiring COVID-19 and specimen was shorter in patients with diffuse ALI (median, 61.5 days) compared with patients with focal (140 days) or no ALI (130 days) (P = .009). Sixteen (of 20; 80%) SARS-CoV-2 reverse transcription droplet digital polymerase chain reaction tests were positive, up to 174 days after COVID-19 onset. Time between COVID-19 onset and most recent computed tomography in patients with consolidation on imaging was shorter (median, 43.0 days) versus in patients without consolidation (87.5 days; P = .02). Reticulations were associated with longer time to computed tomography after COVID-19 onset (median, 82 versus 23.5 days; P = .006). CONCLUSIONS.­: ALI and SARS-CoV-2 RNA can be detected in patients with COVID-19 for many months. ALI may evolve into fibrotic interstitial lung disease.


Assuntos
COVID-19 , Autopsia , COVID-19/complicações , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , RNA Viral , SARS-CoV-2
11.
Thorac Cancer ; 13(7): 925-933, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35194958

RESUMO

INTRODUCTION: Patients with small-cell lung cancer (SCLC) have a very poor prognosis. However, a subset of SCLC achieves long-term survival. The objective of this study was to investigate factors and pattern of long-term survival in patients with limited-stage small cell lung cancer (LS-SCLC) who achieved a complete response (CR) after chemoradiotherapy. PATIENT AND METHODS: This was a single-center retrospective study. The analysis of hazard ratio (HR) and 95% confidence interval (CI) was performed using Cox proportional hazards model. For pattern analysis, the date of recurrence was used as the endpoint. The nominal categorical variables were analyzed by the χ2 test. Survival was estimated using the Kaplan-Meier model, and the results were reported as the median and interquartile range. RESULTS: We identified 162 patients, median age was 64.7 (56.2-70.2) years, and 94 (58%) were females. Eighty-one patients (50%) had recurrence during follow-up. Gastroesophageal reflux disease (GERD) (HR, 0.65; 95% CI, 0.45-0.93; p = 0.016) and neurological paraneoplastic syndrome (PNS) (HR, 0.46; 95% CI, 0.29-0.72; p < 0.001) were independent factors associated with improved overall survival (OS). Patients with GERD had prolonged recurrence free survival (RFS) compared to patients without GERD (median, 29.1 months vs. 13.9 months, p < 0.001), whereas patients with neurological PNS had a reduced recurrence rate compared to those patients without neurological PNS (No. [%], 8 [20.5] vs. 73 [59.3], p < 0.001). CONCLUSIONS: Patients with LS-SCLC achieving a CR after chemoradiotherapy, GERD, and neurological PNS were associated with improved OS. GERD and neurological PNS were associated with longer RFS and lower recurrence rate, respectively.


Assuntos
Refluxo Gastroesofágico , Neoplasias Pulmonares , Síndromes Paraneoplásicas do Sistema Nervoso , Síndromes Paraneoplásicas , Carcinoma de Pequenas Células do Pulmão , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Síndromes Paraneoplásicas/complicações , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/terapia , Taxa de Sobrevida
12.
J Cancer Res Clin Oncol ; 148(8): 2099-2114, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34436667

RESUMO

BACKGROUND: The efficacy of osimertinib in previously EGFR-TKI-treated NSCLC without identification of T790M mutational status remains unclear in real-world practice. PATIENTS AND METHODS: 417 patients had stage III-IV NSCLC harboring EGFR mutation and 154 out of 417 patients receiving osimertinib as ≥ second-line EGFR-TKI were identified. The time to treatment failure and risk of death were analyzed. RESULTS: Higher risk of death was found in EGFR-mutant patients with age ≥ 65 years, non-adenocarcinoma, no surgery or radiation, non-exon 19 deletion/exon 21 L858R, higher ECOG PS (2-4), PD-L1 expression ≥ 50%, and bone/liver/adrenal metastasis (all p < 0.05). Osimertinib as ≥ second-line TKI in patients with/without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib (p = 0.0002; 0.0232, respectively). However, osimertinib-treated patients with T790M did not have superior survival than those without (p = 0.2803). A higher risk of treatment failure for osimertinib was found in males, patients with first-line TKI duration ≤ 12 months, BMI drop > 10%, and PD-L1 expression ≥ 50% (All p < 0.05). Nonetheless, osimertinib as ≥ second-line TKI in patients without identification of 790 M did not have higher risk of treatment failure than those with T790M (p = 0.1236). CONCLUSIONS: This study demonstrates that osimertinib as second line or subsequent TKI in EGFR-TKI-treated patients without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib, in real-world practice. Additionally, EGFR-mutant patients with PD-L1 expression ≥ 50% had a higher risk of treatment failure for osimertinib and worse overall survival than those with PD-L1 expression < 50%. These results suggest that osimertinib as second line or subsequent TKI may be a potential alternative option for the treatment of patients without identification of T790M and PD-L1 expression ≥ 50% is associated with a significantly poor outcome in patients receiving osimertinib.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Acrilamidas , Idoso , Compostos de Anilina/uso terapêutico , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Indóis , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas
13.
Am J Clin Pathol ; 156(6): 989-999, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33978147

RESUMO

OBJECTIVES: Numerous studies on malignant mesothelioma (MM) highlight the prognostic importance of histologic subtype, nuclear grade, and necrosis. This study compares these parameters in paired biopsy and resection specimens of pleural MM. METHODS: Histologic subtype, percentage of epithelioid morphology, nuclear grade, and the presence or absence of necrosis were compared in 429 paired biopsies and resection specimens of pleural MM from 19 institutions. RESULTS: Histologic subtype was concordant in 81% of cases (κ = 0.58). When compared with resection specimens, epithelioid morphology at biopsy had a positive predictive value (PPV) of 78.9% and a negative predictive value (NPV) of 93.5%; sarcomatoid morphology showed high PPV (92.9%) and NPV (99.3%), and biphasic morphology PPV was 89.7% and NPV was 79.7%. Agreement of the percentage of epithelioid morphology was fair (κ = 0.27). Nuclear grade and necrosis were concordant in 75% (κ = 0.59) and 81% (κ = 0.53) of cases, respectively. Nuclear grade showed moderate (κ = 0.53) and substantial (κ = 0.67) agreement from patients with and without neoadjuvant therapy, respectively, and necrosis showed moderate (κ = 0.47 and κ = 0.60) agreement, respectively, in the same subsets of paired specimens. CONCLUSIONS: Paired biopsy-resection specimens from pleural MM show overall moderate agreement in pathologic parameters. These findings may help guide postbiopsy management and triage of patients with MM.


Assuntos
Mesotelioma Maligno , Neoplasias Pleurais , Biópsia , Humanos , Mesotelioma Maligno/patologia , Mesotelioma Maligno/cirurgia , Necrose , Neoplasias Pleurais/patologia , Neoplasias Pleurais/cirurgia , Prognóstico
14.
Pathology ; 53(4): 446-453, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33775406

RESUMO

Diffuse malignant mesothelioma (MM) is an incurable tumour of the serosal membranes, which is often caused by exposure to asbestos and commonly diagnosed at advanced stage. Malignant mesothelioma in situ (MMIS) is now included as diagnostic category by the World Health Organization (WHO). However, our international survey of 34 pulmonary pathologists with an interest in MM diagnosis highlights inconsistency regarding how the diagnosis is being made by experts, despite published guidelines. Whilst the WHO restricts the diagnosis to surgical samples, the very concept has implication for cytological diagnosis, which is already regarded as controversial in itself by some. MMIS is currently only applicable as precursor to MM with an epithelioid component, and raises the possibility for different molecular pathways for different histological MM subtypes. The clinical implications of MMIS at this stage are uncertain, but aggressive therapies are being initiated in some instances. Based on the results of the survey we here present a critical appraisal of the concept, its clinical and conceptual implications and provide practice suggestions for diagnosis. A low threshold for ancillary testing is suggested. The designations of 'malignant mesothelioma, cannot exclude MMIS' or 'atypical mesothelial proliferation with molecular indicators of malignancy, so-called MMIS' could be used on cytology samples, adding 'no evidence of invasion in sample provided' for surgical samples. Clinical and radiological correlation are integral to diagnosis and best done at multidisciplinary meetings. Finally, collaborative studies are required to improve our understanding of MMIS.


Assuntos
Mesotelioma Maligno/diagnóstico , Citodiagnóstico , Diagnóstico Precoce , Humanos , Mesotelioma Maligno/classificação , Mesotelioma Maligno/patologia , Mesotelioma Maligno/terapia , Patologistas , Membrana Serosa/patologia , Inquéritos e Questionários , Organização Mundial da Saúde
15.
Arch Pathol Lab Med ; 145(6): 717-727, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32965489

RESUMO

CONTEXT.­: Idiopathic pulmonary fibrosis is a clinical syndrome characterized by the presence of usual interstitial pneumonia (UIP) radiologically and pathologically. Per consensus criteria adopted in 2011, diagnosis of idiopathic pulmonary fibrosis no longer requires a biopsy in an appropriate context if UIP is seen on imaging. As a result, lung biopsies are now typically reserved for patients having indeterminate clinical or imaging findings or suspicion for alternative diagnoses, but the impact of updated guidelines on pathology practice remains unclear. OBJECTIVE.­: To determine the frequency of histologic UIP before and after 2011. DESIGN.­: Surgical lung biopsies from adults were studied within two 4-year periods: July 1, 2006 through June 30, 2010 and January 1, 2012 through December 31, 2015. Pathology slides were reviewed in a fashion blinded to clinical information and were classified using current guidelines. RESULTS.­: Biopsies from 177 and 86 patients (mean [SD] age, 62 [12] and 59 [14] years; 50.3% [89 of 177] and 48.8% [42 of 86] men) before and after 2011, respectively, were reviewed. Probable UIP or UIP was less-frequently encountered after 2011 in all patients with fibrosis (9 of 54 [16.7%] versus 41 of 119 [34.5%] before 2011, P = .02) and also in patients 50 years old and older (8 of 46 [17.4%] versus 39 of 109 [35.8%] before 2011, P = .02), with a concomitant rise in cases indeterminate for UIP or showing alternative diagnoses. CONCLUSIONS.­: Histology for UIP is less frequently encountered in our contemporary practice compared with the historic era. The pretest probability of a non-UIP diagnosis is now high, even in elderly patients, underscoring the need for pathologists to be familiar with the histologic features of alternative diagnoses.


Assuntos
Consenso , Fibrose Pulmonar Idiopática/diagnóstico , Patologia Cirúrgica/métodos , Guias de Prática Clínica como Assunto , Idoso , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Fibrose Pulmonar Idiopática/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Patologistas/estatística & dados numéricos , Tomografia Computadorizada por Raios X
16.
Am J Surg Pathol ; 45(2): 255-262, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32826527

RESUMO

Only 50% to 70% of patients with mesothelioma report asbestos exposure. Other exposures (eg, radiation) play a role in some cases, but some patients have no obvious cause. We describe a series of patients with long-standing indwelling intra-abdominal shunt catheters who developed malignant peritoneal mesothelioma, suggesting a novel association. We identified 7 patients who had shunts and subsequently developed mesothelioma (5 women; median age: 31 y, range: 18 to 45 y). Clinical history and pathology materials were reviewed, and RNA sequencing was performed. Clinical presentations varied; 6 patients had hydrocephalus and a ventriculoperitoneal shunt, and 1 patient had portal hypertension and a portoatrial shunt. The median duration of shunt therapy in 5 cases was 29 years (range: 12 to 35 y); the remaining 2 patients also had shunts for many years, but specific details were unavailable. Two patients had radiotherapy for malignancies in childhood. One had an alleged exposure to asbestos and 1 had prior exposure to talc. The rest had no known risk factors. Histologically, all tumors were purely epithelioid. Treatments included surgical debulking, chemotherapy, and palliative care. All 7 died of disease (median survival: 7 mo, range: 1 to 18 mo). Molecular testing showed loss of NF2 and CDKN2A/B and a BAP1 mutation in 1 case, and no genomic alterations associated with mesothelioma in 2 cases. Peritoneal mesothelioma may represent a complication of long-standing indwelling shunt catheters. The mechanism is unknown, but chronic peritoneal irritation may play a role. Albeit rare, mesothelioma should be considered in patients with a shunt who present with new ascites.


Assuntos
Cateteres de Demora/efeitos adversos , Mesotelioma Maligno/etiologia , Neoplasias Peritoneais/etiologia , Derivação Portossistêmica Cirúrgica/efeitos adversos , Derivação Ventriculoperitoneal/efeitos adversos , Adolescente , Adulto , Feminino , Humanos , Masculino , Mesotelioma Maligno/patologia , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Adulto Jovem
17.
AJR Am J Roentgenol ; 215(5): 1057-1064, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32877245

RESUMO

OBJECTIVE. The purpose of this article is to characterize the appearance on CT of e-cigarette or vaping product use-associated lung injury (EVALI) in a cohort with histopathologic evidence of this disorder. MATERIALS AND METHODS. Twenty-four patients with EVALI were identified. Chest CT examinations were reviewed by two radiologists for various chest CT findings. For comparison with pathologic findings, CT assessments were distilled into previously described patterns of EVALI seen on CT: acute lung injury (ALI), chronic eosinophilic pneumonia (CEP) or organizing pneumonia (OP), acute eosinophilic pneumonia (AEP), alveolar hemorrhage, hypersensitivity pneumonitis (HP), lipoid pneumonia, and mixed or unclassifiable patterns. RESULTS. Sixteen of 24 (67%) patients were men; the mean age was 34.5 years (range, 17-67 years). The most common CT finding was ground-glass opacities, which was present in 23 of 24 (96%) patients and the dominant finding in 18 of 24 (75%) patients. Consolidation was the next most common finding in 42% of patients. Interlobular septal thickening was present in 29%. Lobular low attenuation was conspicuous in six patients. Distribution was multifocal in 54% of patients, peripheral in 17%, and centrally predominant in 8%. Subpleural sparing was seen in 45%. The predominant CT pattern was ALI (42%), concordant with histopathologic findings in 75%; the next most predominant pattern was ground-glass opacity centrilobular nodules resembling HP (33%). A CT pattern of CEP or OP was seen in 13% of patients, all showing ALI on lung biopsy. No patient showed macroscopic lung parenchymal fat. Two patients with CT ALI patterns showed OP on histopathologic examination. Of the eight patients with ground-glass opacity centrilobular nodules resembling HP at CT, none showed HP at histopathologic examination. CONCLUSION. EVALI manifests at CT as ALI with multifocal ground-glass opacity, often with organizing consolidation, and a small centrilobular nodular pattern resembling HP.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/etiologia , Tomografia Computadorizada por Raios X , Vaping/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Lesão Pulmonar/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
18.
Arch Pathol Lab Med ; 144(12): 1477-1489, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32614648

RESUMO

CONTEXT.­: Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) requires multidisciplinary diagnosis that includes clinical, radiologic, and often pathologic assessment. In 2018, the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and the Latin American Thoracic Society (ATS/ERS/JRS/ALAT) and the Fleischner Society each published guidelines for the diagnosis of IPF, which include criteria for 4 categories of confidence of a histologic usual interstitial pneumonia (UIP) pattern. OBJECTIVE.­: To (1) identify the role of the guidelines in pathologic assessment of UIP; (2) analyze the 4 guideline categories, including potential areas of difficulty; and (3) determine steps the Pulmonary Pathology Society and the greater pulmonary pathology community can take to improve current guideline criteria and histopathologic diagnosis of interstitial lung disease. DATA SOURCES.­: Data were derived from the guidelines, published literature, and clinical experience. CONCLUSIONS.­: Both guidelines provide pathologists with a tool to relay to the clinician the likelihood that a biopsy represents UIP, and serve as an adjunct, not a replacement, for traditional histologic diagnosis. There are multiple challenges with implementing the guidelines, including (1) lack of clarity on the quantity and quality of histologic findings required, (2) lack of recognition that histologic features cannot be assessed independently, and (3) lack of guidance on how pathologists should incorporate clinical and radiographic information. Current criteria for "probable UIP" and "indeterminate for UIP" hinder accurate reflection of the likelihood of IPF. These challenges highlight the need for further morphologic-based investigations in the field of pulmonary pathology.


Assuntos
Fibrose Pulmonar Idiopática/patologia , Doenças Pulmonares Intersticiais/patologia , Guias de Prática Clínica como Assunto , Biópsia , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Patologistas
19.
Am J Ind Med ; 63(9): 821-827, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32597538

RESUMO

Workers in a print shop are exposed to photocopier toner dust and paper dust over a prolonged period of time. However, there are only rare case reports of toner and paper dust induced lung damage in humans. We reviewed our consultation files for a period of 30 years from 1987 to 2018 to look for cases with a diagnosis of giant cell interstitial pneumonia (GIP), printer toner exposure and paper dust exposure resulting in lung disease. There were two cases which met our inclusion criteria. Slides, clinical histories and imaging were reviewed. Both the patients had worked in print shops, and had no history of exposure to hard metals. Patient 1 presented with shortness of breath and cough over several months, while patient 2 was asymptomatic at presentation. Both the patients underwent surgical lung biopsies. Histopathologic examination from both the cases showed a spectrum of pathology, including features of GIP, desquamative interstitial pneumonia, chronic bronchiolitis with lymphoid hyperplasia, and particulate matter consistent with toner. Energy dispersive spectroscopy was performed on one case, and it revealed no cobalt or tungsten particles. The unusual combination of findings is very suggestive that toner particles with or without paper dust exposure were responsible for the pathologic changes in the lungs of these patients. This possibility should be explored further with additional patients who work in print shops where they are exposed to paper dust and paper toner and have signs or symptoms of diffuse lung disease.


Assuntos
Poeira , Tinta , Exposição Ocupacional/efeitos adversos , Papel , Pneumoconiose/etiologia , Impressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Arch Pathol Lab Med ; 144(12): 1490-1500, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32401055

RESUMO

CONTEXT.­: Vaping is the inhalation of heated aerosol from a small battery-powered device as a method to deliver nicotine or other substances. A recent outbreak of severe respiratory illness primarily in the United States has put a spotlight on vaping and its potential risks. OBJECTIVE.­: To familiarize pathologists with vaping, the cytologic and histopathologic features of vaping-associated acute lung injury, and the role of pathology in this diagnosis. DATA SOURCES.­: A targeted literature review was performed. CONCLUSIONS.­: Most cases of vaping-associated lung injury have been linked to vaping products containing tetrahydrocannabinol or other cannabinoids. Lung biopsies show a spectrum of nonspecific acute lung injury patterns (organizing pneumonia, diffuse alveolar damage, acute fibrinous, and organizing pneumonia, or combinations of the above), accompanied by prominent, foamy macrophage accumulation. Injury is usually accentuated around small airways. Lipid-laden macrophages can be identified in bronchioloalveolar lavage fluid in most patients and these can be highlighted using lipid stains, such as oil red O, but the clinical utility of this finding remains unclear, as lipid-laden macrophages can be seen in a wide variety of processes and should not be relied upon to make the diagnosis. Classic histologic features of exogenous lipoid pneumonia have not been identified in tissue samples. Lightly pigmented macrophages, similar to those seen with traditional cigarette smoking, are present in some cases but are usually a minor feature. To date, no specific pathologic features for vaping-related injury have been identified, and it remains a diagnosis of exclusion that requires clinicopathologic correlation.


Assuntos
Lesão Pulmonar Aguda/patologia , Canabinoides/efeitos adversos , Sistemas Eletrônicos de Liberação de Nicotina , Fumar/efeitos adversos , Vaping/efeitos adversos , Lesão Pulmonar Aguda/etiologia , Biópsia , Agonistas de Receptores de Canabinoides/efeitos adversos , Dronabinol/efeitos adversos , Humanos , Pulmão/patologia , Macrófagos/patologia , Patologistas
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