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Pulmonary large-cell carcinoma-a diagnostically and clinically controversial entity-is defined as a non-small-cell carcinoma lacking morphologic differentiation of either adenocarcinoma or squamous cell carcinoma, but suspected to represent an end stage of poor differentiation of these tumor types. Given the recent advances in immunohistochemistry to distinguish adenocarcinoma and squamous cell carcinoma, and the recent insights that several therapeutically relevant genetic alterations are distributed differentially in these tumors, we hypothesized that immunophenotyping may stratify large-cell carcinomas into subsets with distinct profiles of targetable driver mutations. We therefore analyzed 102 large-cell carcinomas by immunohistochemistry for TTF-1 and ΔNp63/p40 as classifiers for adenocarcinoma and squamous cell carcinoma, respectively, and correlated the resulting subtypes with nine therapeutically relevant genetic alterations characteristic of adenocarcinoma (EGFR, KRAS, BRAF, MAP2K1/MEK1, NRAS, ERBB2/HER2 mutations and ALK rearrangements) or more common in squamous cell carcinoma (PIK3CA and AKT1 mutations). The immunomarkers classified large-cell carcinomas as variants of adenocarcinoma (n=62; 60%), squamous cell carcinoma (n=20; 20%) or marker-null (n=20; 20%). Genetic alterations were found in 38 cases (37%), including EGFR (n=1), KRAS (n=30), BRAF (n=2), MAP2K1 (n=1), ALK (n=3) and PIK3CA (n=1). All molecular alterations characteristic of adenocarcinoma occurred in tumors with immunoprofiles of adenocarcinoma or marker-null, but not in tumors with squamous immunoprofiles (combined mutation rate 50% vs 30% vs 0%, respectively; P<0.001), whereas the sole PIK3CA mutation occurred in a tumor with squamous profile (5%). Furthermore, marker-null large-cell carcinomas were associated with significantly inferior disease-free (P<0.001) and overall (P=0.001) survival. In conclusion, the majority (80%) of large-cell carcinomas can be classified by immunomarkers as variants of adenocarcinoma or squamous cell carcinoma, which stratifies these tumors into subsets with a distinct distribution of driver mutations and distinct prognoses. These findings have practical implications for diagnosis, predictive molecular testing and therapy selection.
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Biomarcadores Tumorais/genética , Carcinoma de Células Grandes/genética , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/genética , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células Grandes/classificação , Carcinoma de Células Escamosas/genética , Feminino , Genótipo , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
Retinoblastoma is the most common primary cancer of the eye in children. The incidence of second tumors in survivors of bilateral retinoblastoma and in survivors of unilateral retinoblastoma who presumably carry a germline RB1 mutation is documented. This article describes the previously unrecognized association of sinonasal adenocarcinoma as a second malignancy in retinoblastoma survivors. We present three cases who received radiation therapy as a part of their treatment and developed sinonasal adenocarcinoma as a second malignancy. Sinonasal adenocarcinoma should be considered as a second malignancy in retinoblastoma survivors who present with vague sinus symptoms.
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Adenocarcinoma/patologia , Neoplasias Induzidas por Radiação/patologia , Segunda Neoplasia Primária/patologia , Neoplasias Nasais/patologia , Neoplasias dos Seios Paranasais/patologia , Retinoblastoma/radioterapia , Adenocarcinoma/etiologia , Adulto , Idoso , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/etiologia , Neoplasias dos Seios Paranasais/etiologia , Radioterapia/efeitos adversos , SobreviventesRESUMO
OBJECTIVE: The BRAF V600E mutation has been associated with aggressive disease in papillary thyroid carcinoma (PTC). Molecular testing has been proposed as a useful adjunct to cytology in the diagnosis of malignancy and for tailoring clinical management. The aims of our study were to evaluate the BRAF mutational status using archived fine-needle aspiration biopsy (FNAB) material from patients with long-term follow-up and to correlate it with the original cytology diagnosis, clinicopathological stage at surgery, and prognosis. STUDY DESIGN: FNAB material from 52 cases of PTC, with a mean follow-up of 8.4 years, was used in this study. DNA was extracted from archival cytology slides. Mutation analysis was performed by standard sequencing and locked nucleic acid-PCR/sequencing. RESULTS: The BRAF V600E mutation was present in 46% of cases, but it was absent in all FNABs diagnosed originally as atypical and in 14 of 17 suspicious cases. Recurrence was significantly more frequent (p = 0.006) in cases with BRAF mutations and 54% of these cases presented with stage 2 or higher. CONCLUSION: The BRAF V600E mutation is associated with a higher pathological stage at surgery and a higher rate of recurrence. BRAF mutation analysis did not provide a significant increase in the accuracy of thyroid FNABs diagnosed as suspicious or atypical in our institution.
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Carcinoma/diagnóstico , Carcinoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Carcinoma/patologia , Carcinoma/cirurgia , Carcinoma Papilar , Criança , Análise Mutacional de DNA , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Recidiva , Estudos Retrospectivos , Risco , Câncer Papilífero da Tireoide , Glândula Tireoide/metabolismo , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) represents a standardized reporting system for salivary gland lesions. The recent literature has demonstrated a wide range of data regarding range of malignancy (ROM) and interobserver variability. The objective of the current study was to evaluate the reproducibility and interobserver agreement of MSRSGC, and establish the ROM in a unique patient population residing within a designated Health Professional Shortage Area. METHODS: A total of 380 salivary gland fine-needle aspiration cases were obtained over a 3-year period. Corresponding cytology reports and slides were reviewed in a blinded fashion by a panel of cytopathologists and recategorized using MSRSGC. ROM was calculated by cytohistologic correlation in 176 cases. Agreement between review of reports and slides and interobserver reliability were determined using kappa statistics. RESULTS: The ROMs per MSRSGC category based on review of reports and slides were as follows: 4% and 0%, respectively, for nonneoplastic; 22% and 0%, respectively, for nondiagnostic; 42.9% and 48%, respectively, for atypia of undetermined significance; 1.6% and 1.9%, respectively, for benign-neoplastic; 17.9% and 15.6%, respectively, for salivary gland neoplasm of uncertain malignant potential; 81.8% and 71.4%, respectively, for suspicious for malignancy; and 100% and 90.5%, respectively, for malignant. There was a 59.2% overall agreement between review of reports and slides with regard to recategorizing salivary gland lesions (kappa, 0.51). The interobserver reliability demonstrated a 64.6% agreement (weighted kappa, 0.59). CONCLUSIONS: The ROMs at the study institution appeared comparable to those in the published literature. There was moderate overall agreement among cytopathologists and low interobserver agreement with regard to the indeterminate categories. Image-guided fine-needle aspiration specimens; rapid onsite adequacy; and integration of clinical, imaging, and ancillary studies can improve diagnostic accuracy among indeterminate lesions.
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Neoplasias das Glândulas Salivares/diagnóstico , Glândulas Salivares/patologia , Centros de Atenção Terciária/organização & administração , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologia , Adulto JovemRESUMO
The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.
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Cercariform cells are slender cells with a bulbous end and a unipolar long cytoplasmic process, resembling Schistosoma cercariae. Since their first description in urothelial carcinoma, multiple studies have attempted to explore their utility in distinguishing metastatic urothelial carcinoma from other common malignant neoplasms, such as adenocarcinoma and squamous-cell carcinoma. Although not pathognomonic, they are most commonly encountered in urothelial carcinoma, but they can also be seen in other neoplasms, raising the possibility that this cytomorphological feature can be exploited to aid in diagnosis.
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Carcinoma/patologia , Esquistossomose/patologia , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Idoso , Diagnóstico Diferencial , Humanos , MasculinoRESUMO
BACKGROUND: Primary carcinoid tumors of the liver are uncommon and rarely symptomatic. The diagnosis of primary hepatic etiology requires rigorous workup and continued surveillance to exclude a missed primary. CASE PRESENTATION: We present a case of a 62-year-old female with a primary hepatic carcinoid tumor successfully resected, now with three years of disease-free follow-up. We present a review of the current literature regarding the diagnosis, pathology, management, and natural history of this disease entity. CONCLUSION: Primary carcinoid tumors of the liver are rare, therefore classifying their nature as primary hepatic in nature requires extensive workup and prolonged follow-up. All neuroendocrine tumors have an inherent malignant potential that must be recognized. Management remains surgical resection, with several alternative options available for non-resectable tumors and severe symptoms. The risk of recurrence of primary hepatic carcinoid tumors after resection remains unknown.
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Tumor Carcinoide/diagnóstico , Tumor Carcinoide/cirurgia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
A 47-year-old man with a history of dyshidrotic eczema presented to the emergency department with diffuse erythema, chills and pruritus of three weeks' duration. The patient had received two injections of methotrexate in the preceding two weeks, both of which had failed to improve his whole-body erythema and pruritus. In the emergency department, the patient was evaluated for infection and admitted for the dermatology consultation. After being seen on the general medical floor by the dermatology service the diagnosis of erythroderma was made and the patient was treated with intravenous (IV) cyclosporine therapy, with which his rash dramatically improved over three days. This case report summarizes the presentation and differential of erythroderma, and highlights the importance of having a high index of suspicion for this potentially fatal disease.
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Fluoroscopy-guided transbronchial forceps biopsy has a low diagnostic yield in patients with radiographic suspicion of interstitial lung disease. Cryobiopsy has a higher diagnostic yield likely due to preserved lung architecture and larger biopsies; however, there is an increased risk of major airway bleeding and pneumothorax. Simultaneous use of endobronchial balloon blocker allows for containment of bleeding after cryobiopsy to the affected lobe. In the current article we describe use of radial ultrasound in identification of a target lung parenchyma without a major blood vessel adjacent to distal bronchi. After fluoroscopic marking of the selected airway a 3 second cryobiopsy was performed after localization of cryoprobe. Simultaneous use of radial ultrasound and fluoroscopy can possibly decrease bleeding complication associated with cryobiopsy in patients with suspected interstitial lung disease.
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Broncoscopia/efeitos adversos , Criocirurgia/efeitos adversos , Doenças Pulmonares Intersticiais/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluoroscopia/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia/instrumentaçãoRESUMO
More than 40 years ago Lynch et al. described several multigenerational breast cancer family pedigrees which demonstrated autosomal dominant inheritance of a trait(s) that increased risks for both breast and ovarian cancers. Mutation carriers in at least 90 % of these hereditary breast ovarian cancer (HBOC) syndrome families have been linked to cancer-associated mutations in the genes BRCA1 and BRCA2. This review focuses on the contributions of Lynch, colleagues and collaborators and pertinent literature, toward defining the HBOC syndrome, the cancer risks that the inherited adverse mutations convey, the gynecologic tissues and organs from which the malignancy may arise to disseminate throughout the pelvic and abdominal organs and peritoneum and how this information can be used to reduce the risk and morbidities of intra-abdominal carcinomatosis in effected individuals.
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Neoplasias Abdominais/prevenção & controle , Carcinoma/prevenção & controle , Predisposição Genética para Doença , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Tumor Mulleriano Misto/prevenção & controle , Procedimentos Cirúrgicos Profiláticos/métodos , Neoplasias Abdominais/genética , Neoplasias Abdominais/patologia , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma/genética , Carcinoma/patologia , Feminino , Síndrome Hereditária de Câncer de Mama e Ovário/patologia , Síndrome Hereditária de Câncer de Mama e Ovário/cirurgia , Humanos , Tumor Mulleriano Misto/genética , Tumor Mulleriano Misto/patologia , Mutação , Ovariectomia , Mastectomia Profilática , SalpingectomiaRESUMO
Henoch Schonlein purpura (HSP) is an immune mediated disease associated Immunoglobulin A (IgA) deposition within the affected organs. While the disease is commonly seen in the pediatric age group, it is rarely seen in adults. We report the case of a 93-year-old Caucasian lady who presented with nonthrombocytopenic purpuric rash and acute kidney injury after an episode of bronchitis. Rapid and progressive deterioration of renal function prompted a kidney biopsy, which showed findings consistent with IgA nephropathy confirming the diagnosis of HSP. The patient was treated with high dose intravenous methylprednisolone followed by oral prednisone; however, her kidney disease progressed to end stage renal disease requiring hemodialysis. HSP is usually a self-limiting disease in children. However, adults are at an increased risk of severe renal involvement including end stage renal disease. Purpuric skin rash with renal involvement should raise suspicion for HSP. This is the oldest known patient with HSP.