Incidence and aetiologies of pulmonary granulomatous inflammation: a decade of experience.

BACKGROUND AND OBJECTIVE: Granulomatous lung disease (GLD) is caused by a wide range of conditions. Often there is a need to correlate pathological findings with clinical, microbiological or radiological data to determine an aetiology. The aim of this study was to determine the different aetiologies of GLD over the past decade. METHODS: Among 2228 consecutive lung specimens from 1999 to 2011, 226 cases (10.1%) were positive for GLD. One hundred ninety patients were retrospectively reviewed and diagnoses were assigned based on availability of histological/clinical/microbiological correlation. RESULTS: A confident, probable and uncertain diagnosis was made in 68.4%, 13.2% and 18.4% patients. The aetiologies comprised infectious, non-infectious and uncertain in 54.7%, 26.8% and 18.4% patients. Mycobacterial infections constituted 27% of all patients, and included atypical, tuberculous and unclassified mycobacteria in order of frequency. Acid-fast bacilli (AFB) were visualized in tissue sections in 29% cases and cultured in 73% cases. Fungal infections comprised 27% of all cases, which included Coccidioides, Cryptococcus, Aspergillus and Histoplasma in order of frequency. Fungi were visualized in tissue sections with Gomori methenamine silver (GMS) stain in 83% patients and cultured in 52% cases. Sarcoidosis was the major non-infectious aetiology, constituting 21% of all patients. Necrosis in granulomas was associated with the presence of infection (P < 0.001). CONCLUSIONS: The aetiology in necrotizing GLD with negative AFB and GMS stains is most likely infectious due to atypical mycobacteria. Coccidioidomycosis was the most common fungal infection. The aetiology in non-necrotizing GLD is most likely non-infectious, probably sarcoidosis.

Two cases of endobronchial carcinoid masked by superimposed aspergillosis: a review of the literature of primary lung cancers associated with Aspergillus.

We describe 2 cases of endobronchial pulmonary carcinoid tumor with superimposed Aspergillus colonization. The Aspergillus hyphae were associated with fibrin, ulcer debris, and granulomatous inflammation in part masking the carcinoid tumor. Presence of necrotic debris made diagnosis on biopsy difficult, and atypical carcinoid could not be ruled out. The association of carcinoid tumor with aspergillosis is rare and has been reported in 4 other cases thus far. A review of the literature reveals at least 35 cases of lung carcinoma with coexisting Aspergillus upon presentation. Most of these carcinomas are either cavitary squamous cell or adenocarcinomas harboring an aspergilloma. The other carcinomas are associated with bronchial obstruction as in carcinoids or are a minor component of a preexisting cavity raising the possibility of "scar carcinoma." As in aspergillomas not associated with carcinoma, upper lobe involvement predominates. Diagnosis can be challenging with delayed discovery of underlying neoplasm leading to suboptimal treatment.

Cystic lung lesions in Sjogren syndrome: analysis of lymphocyte subsets in tissue with clinico-radiologic-pathologic correlation.

Pulmonary complications associated with Sjögren syndrome (SS) have attracted attention in recent years. Sjögren syndrome has been associated with small cyst formation in salivary glands, thymus, and lungs and has been recently brought to the forefront by radiologists due to high-resolution techniques. However, pathologists are less aware of this finding unless clinico-radiologic-pathologic correlation is sought. Formation of large bullae in SS is a rare complication with potential for confusion with other diseases. Here, we present the clinical, radiologic, and pathologic findings in 3 patients with SS associated with multiple pulmonary cystic lesions. All 3 patients had a variable mixed restrictive and obstructive component of the disease. There was good correlation with the pulmonary function tests (PFTs), high-resolution computed tomographic scan, and morphology with regard to the restrictive component. The small cysts appear to correlate with the extent of obstructive changes on the PFTs. However, the large bullae do not, implying noncommunication with the conducting airways. This noncorrelation between the PFTs and extent of bullous disease with predominant involvement of lower lobes in SS enables distinction from bullous emphysema. The mechanism of bulla formation in SS appears to be different from bullous emphysema. A check valve mechanism has been proposed previously in SS, which does not explain cyst formation in the thymus. Alternately, inflammation may play a role with the key suspects being CD4 T-helper cells and perhaps NK cells. This is the first report of a clinico-radiologic-pathologic correlation with analysis of lymphocyte subsets.

Aß Amyloid Scaffolds the Accumulation of Matrisome and Additional Proteins in Alzheimer's Disease.

We report a highly significant correlation in brain proteome changes between Alzheimers disease (AD) and CRND8 APP695NL/F transgenic mice. However, integrating protein changes observed in the CRND8 mice with co-expression networks derived from human AD, reveals both conserved and divergent module changes. For the most highly conserved module (M42, matrisome) we find many proteins accumulate in plaques, cerebrovascular amyloid (CAA), dystrophic processes, or a combination thereof. Overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), in CRND8 mice brains leads to increased accumulation of A ß ; in plaques and in CAA; further, recombinant MDK and PTN enhance A ß ; aggregation into amyloid. Multiple M42 proteins, annotated as heparan sulfate binding proteins, bind to fibrillar A ß 42 and a non-human amyloid fibril in vitro. Supporting this binding data, MDK and PTN co-accumulate with transthyretin (TTR) amyloid in the heart and islet amyloid polypeptide (IAPP) amyloid in the pancreas. Our findings establish several critical insights. Proteomic changes in modules observed in human AD brains define an A ß ; amyloid responsome that is well conserved from mouse model to human. Further, distinct amyloid structures may serve as scaffolds, facilitating the co-accumulation of proteins with signaling functions. We hypothesize that this co-accumulation may contribute to downstream pathological sequalae. Overall, this contextualized understanding of proteomic changes and their interplay with amyloid deposition provides valuable insights into the complexity of AD pathogenesis and potential biomarkers and therapeutic targets.

Genetics and imaging of hepatocellular adenomas: 2011 update.

Hepatocellular adenomas are benign liver neoplasms with specific but varied histopathologic findings and tumor biology. The results from recent studies of the pathologic and genetic basis of hepatocellular adenomas provide important insights into the pathogenesis and molecular changes, as well as the putative oncologic pathways used by diverse adenoma subtypes. On the basis of the genetic and pathologic features, hepatocellular adenomas are categorized into three distinct subtypes: (a) inflammatory hepatocellular adenomas, (b) hepatocyte nuclear factor 1 α-mutated hepatocellular adenomas, and (c) ß-catenin-mutated hepatocellular adenomas. Different subtypes show variable clinical behavior, imaging findings, and natural history, and thus the options for treatment and surveillance may vary. Cross-sectional imaging plays an important role in the diagnosis, subtype characterization, identification of complications, and surveillance of hepatocellular adenomas. New schemas for genotype-phenotype classification of hepatic adenomas, as well as management triage of patients with specific subtypes of adenomas, are being proposed in an attempt to improve clinical outcomes.

Current update on borderline ovarian neoplasms.

OBJECTIVE: Borderline ovarian tumors comprise a unique group of noninvasive ovarian neoplasms with characteristic histology and variable tumor biology that typically manifest as low-stage disease in younger women with resultant excellent prognosis. CONCLUSION: Borderline tumors are considered to be precursors of low-grade ovarian cancers. Accurate diagnosis and staging facilitate optimal patient management particularly in patients desiring to preserve fertility.

Comprehensive update on select immune-mediated gastroenterocolitis syndromes: implications for diagnosis and management.

There is a heterogeneous group of noninfectious gastroenterocolitis syndromes that are characterized by immune dysregulation. Recent advances in pathologic analysis have allowed for better characterization of many of these disorders. Some entities demonstrate characteristic disease distribution, epidemiologic features, natural history, and response to specific therapy. For instance, celiac disease occurs in genetically susceptible individuals who are sensitive to gluten, eosinophilic esophagitis is an immune response to ingested allergens, and microscopic colitis predominantly occurs in older patients with chronic diarrhea and is induced or exacerbated by drugs. Eosinophilic gastroenteritis has a variety of clinical and imaging manifestations. Crohn disease and ulcerative colitis are multifactorial immune-mediated chronic inflammatory disorders and have become increasingly prevalent in recent years. Multidetector computed tomography and magnetic resonance imaging provide valuable information that may be used to diagnose these conditions, guide treatment, and assess changes after treatment, and the role of imaging in evaluating response to therapy continues to evolve and expand.

Pulmonary Adenocarcinoma, Intra-alveolar Variant: A Rare Entity Mimicking Desquamative Interstitial Pneumonia.

Exclusive discohesive tumor cells within intra-alveolar spaces is a rare pattern of involvement of primary and metastatic lung tumors. In the absence of a tumoral mass, this pattern closely mimics desquamative interstitial pneumonia (DIP) clinically, radiologically, and histologically. However, a secondary DIP pattern may be seen adjacent to a tumor mass not infrequently. Here, we describe a case of a 64-year-old woman status post bilateral lung transplantation, who was radiologically thought to have an interstitial lung disease. The autopsy lung specimen revealed extensive involvement by intra-alveolar adenocarcinoma, with a cytomorphology mimicking alveolar macrophages as seen in DIP in the absence of a tumoral mass. The presence of subtle clustering with signet ring cell features and rare micropapillae were an important clue to the diagnosis. The tumor cells were positive for CK7, napsin-A, and TTF-1, and negative for CD68. This case represents an unusual variant of pulmonary adenocarcinoma with a pure intra-alveolar pattern of involvement, mimicking DIP. To the best of our knowledge, excluding biopsy specimens, only one similar case has been reported in the literature and none in the posttransplant setting.

Chondrosarcoma-like metastasis from a poorly differentiated uterine cervical squamous cell carcinoma. A unique morphology and diagnostic pitfall in cytology.

Rare cases of metastatic squamous cell carcinoma with chondroid differentiation from esophageal primary have been reported but none from the uterine cervix. Given the rarity of this phenomenon and potential diagnostic pitfall, we present this unusual case. The patient is a 25-year-old woman who presented with shortness of breath. Computerized tomography (CT) showed several lung and pleural-based nodules. CT-guided core biopsy with touch preparations were performed on the pleural-based nodule. The touch preparations showed large, spindle-to-oval shaped cells with pleomorphic nuclei embedded in metachromatic chondroid stroma. The core biopsies also showed predominantly round-to-spindle shaped cells with hyperchromatic nuclei and prominent nucleoli embedded in a cartilaginous matrix. Her past medical history is significant for a poorly differentiated squamous cell carcinoma of the cervix, which on review showed a typical non-keratinizing squamous cell carcinoma without sarcomatous differentiation. Immunohistochemical stains performed on the pleural-based mass showed tumor positivity for AE1/AE3, CK5/6, p16, and S-100. Similar results were seen when the cervical tumor was stained retrospectively. Human papilloma virus (HPV) in situ hybridization performed on both the pleural-based mass and cervical tumor detected the presence of high-risk HPV subtypes including 16 and 18. These findings supported a lung metastasis from the prior cervical carcinoma. This case emphasizes that cervical carcinoma can develop mesenchymal (chondrosarcomatous) differentiation in metastasis even in tumors presenting with pure epithelial phenotype. Awareness of this occurrence especially on limited cytology material, knowledge of the prior history and use of ancillary tests are extremely helpful in arriving at the correct diagnosis. Diagn. Cytopathol. 2017;45:750-753. © 2017 Wiley Periodicals, Inc.

Mice deficient for N-ras: impaired antiviral immune response and T-cell function.

Ras proteins have a key role in the regulation of several cellular functions, and are involved in a significant percentage of human tumors. However, the specific functions of the different Ras isoforms are poorly understood. In this work, we show for the first time a specific role for N-ras in T-cell function and development. Mice defective for N-ras have low numbers of CD8 single positive thymocytes and decreased thymocyte proliferation in vitro. In Ras signaling and activation assays, KO-N-ras thymocytes showed a defective response to T-cell activation. In turn, these deficiencies resulted in a significant reduction in the production of interleukin 2 on thymocyte activation. We have also detected in vivo the functional consequences of N-ras deficiency. KO-N-ras mice showed an increased sensitivity to influenza infection, especially when low doses of virus were used. Finally, we have detected an abnormal activation pattern of downstream Ras molecules in T-cell receptor-activated KO-N-ras thymocytes that is consistent with the defective T-cell function found in these animals. All of the results derived from this work constitute a significant contribution to the knowledge of N-ras-specific functions.

Breast adenomyoepithelioma and adenomyoepithelioma with carcinoma (malignant adenomyoepithelioma) with associated breast malignancies: A case series emphasizing histologic, radiologic, and clinical correlation.

The 2012 World Health Organization (WHO) classification of breast tumors distinguishes adenomyoepitheliomas (AMEs) as benign tumors composed of a biphasic proliferation of phenotypically variable myoepithelial cells around small epithelial lined spaces. Many AMEs have demonstrated benign behavior and are often cured with excision with negative margins, but some have exhibited malignant transformation of the myoepithelial cells, ductal epithelial cells, or both. When one of the components is histologically malignant, it is termed AME with carcinoma. Due to the rarity, the literature correlating imaging, histology, and clinical outcome is limited. A retrospective review was undertaken. A review of an institutional pathology database identified 14 cases with AME or malignant AME. Most AMEs had nonspecific imaging findings and were categorized as Bi-Rads 4. Histologic features of AME did not correlate with prior or concurrent breast malignancies or any radiographic features. Clinical follow up could be obtained for all but one case (mean follow up time = 75 months). 5 cases had no known treatment post-biopsy and 5 patients received mastectomy. No recurrences were noted. 3/13 cases of benign AME had associated breast malignancies including invasive ductal adenocarcinoma and ductal carcinoma in-situ. 1 case of malignant AME had a synchronous separate malignant phyllodes tumor. Given the unclear and unpredictable propensity for malignant transformation, conservative excision with negative margins currently seems appropriate.

CD44 Expression Level and Isoform Contributes to Pancreatic Cancer Cell Plasticity, Invasiveness, and Response to Therapy.

PURPOSE: A subpopulation of pancreatic ductal adenocarcinoma (PDAC) cells is thought to be inherently resistant to chemotherapy or to give rise to tumor cells that become resistant during treatment. Here we determined the role of CD44 expression and its isoforms as a marker and potential target for tumor cells that give rise to invasive and gemcitabine-resistant tumors. EXPERIMENTAL DESIGN: RT-PCR, Western blotting, and DNA sequencing was used to determine CD44 isoform and expression levels. Flow cytometry was used to sort cells on the basis of their CD44 expression level. CD44 expression was knocked down using shRNA. Tumorigenic properties were determined by clonogenic and Matrigel assays, IHC, tumor growth in vivo using luciferase imaging and by tumor weight. RESULTS: We identified an invasive cell population that gives rise to gemcitabine-resistant tumors. These cancer cells express a high level of CD44 standard isoform and have an EMT phenotype (CD44s/EMT). In vivo, CD44s/EMT engraft and expand rapidly and give rise to tumors that express high levels of CD44 isoforms that contain multiple exon variants. CD44low-expressing cells show continued sensitivity to gemcitabine in vivo and knockdown of CD44 in CD44s/EMT cells increases sensitivity to gemcitabine and decreases invasiveness. CONCLUSIONS: PDAC cells expressing high levels of CD44s with a mesenchymal-like phenotype were highly invasive and developed gemcitabine resistance in vivo Thus, initial targeting CD44 or reversing the CD44high phenotype may improve therapeutic response. Clin Cancer Res; 22(22); 5592-604. ©2016 AACR.

Detection of KSHV in transbronchial biopsies in patients with Kaposi sarcoma.

In transbronchial biopsies, Kaposi sarcoma (KS) is difficult to correctly diagnose by H&E staining due to the inherent vascular nature of the lung tissue, coupled with the subtle nature of the changes in early KS. Since KS-associated herpesvirus (KSHV) has been found in all clinical forms of KS, the detection of KSHV genomic DNA sequences and/or viral products may be helpful in the diagnosis of pulmonary KS. From their files during the past 10 years, the authors identified ten HIV/AIDS patients who were positive for KS in transbronchial biopsies and four HIV/AIDS patients with KS-negative transbronchial biopsies. Immunohistochemistry with antibodies against the latency-associated nuclear antigen (LANA-1 or LNA) of KSHV was performed. Nested polymerase chain reactions (PCR) with KSHV ORF-K1 or -K9 were performed in all cases, and the KSHV sequences were detected in 9/10 (90%) KS cases. Immunohistochemical analysis was able to detect 4/10 (40%) cases. One case was negative by both PCR and immunohistochemistry. Of the five KS cases that were not diagnosed definitively ("consistent with" or "suspicious for"), two were confirmed by both immunoreactivity and PCR. One of the negative control cases was positive for KSHV by PCR but not by immunohistochemistry. The patient was thereafter found to have a clinical history of pulmonary KS at another hospital. In conclusion, in transbronchial biopsies of the lung suspicious for KS, PCR is the most sensitive technique available for clinical diagnosis of KS. Immunohistochemistry analysis might be helpful in difficult pulmonary KS cases.

Cytologic findings of NUT midline carcinoma in the hilum of the lung.

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a clinically lethal malignancy affecting all age group often located in the midline structures such as mediastinum, larynx and nasopharynx. It is characterized by chromosomal translocation between chromosomes 15 and 19 with the formation of chimeric gene BRD-NUT. We present the cytologic findings of NMC including the immunohistochemical stains performed. The patient is a 34-year-old man who presented with 1 month history of dyspnea and interscapular pain followed by nonproductive cough a week before consultation. He was initially diagnosed with pneumonia. Due to progression of symptoms, a chest CT scan was performed revealing a large hilar mass and mediastinal adenopathy. A core biopsy with touch preparations of the hilar mass was performed which revealed cohesive malignant cells with ovoid to elongated nuclei, fine to coarse chromatin pattern, irregular nuclear contour, prominent nucleoli, and scant ill-defined cytoplasm arranged in sheets and focally pseudoglandular pattern. Although focal nuclear overlapping and crush artifact were identified, karyorrhectic debris and mitotic figures were rare. Squamous differentiation was absent. The core biopsy showed discohesive malignant cells with tumor necrosis. No nuclear molding, glandular or squamous differentiation was identified. The tumor was immunoreactive for p63 and NUT with high Ki-67 (>80%). The tumor was negative for keratin, lymphoid, myeloid, neuroendocrine markers and S-100. This case emphasizes that cytologic features of NMC can mimic poorly differentiated, undifferentiated and neuroendocrine carcinomas and the importance of immunohistochemical stains especially NUT monoclonal antibody in arriving at the diagnosis.

Thymic carcinoma: state of the art review.

Thymic carcinoma is a rare neoplasm with distinct clinical and pathological characteristics. The prognosis is often poor with an aggressive course that belies its numerical rarity. Potentially prognostic factors for survival include histopathologic grade, clinical stage, and resectability of the tumor. Five-year survival rates for all patients are approximately 30-50%, with a significant survival time differential between low-grade and high-grade neoplasms. Owing to the paucity of cases, optimal management of thymic carcinoma has yet to be defined. At present, a multimodality approach involving aggressive surgical resection, platinum-based combination chemotherapeutic interventions, and radiotherapy represent the preferred therapeutic approach. Though our knowledge remains somewhat speculative at present, several scientific, technological and therapeutic innovations may have a potentially significant impact on the future of this disease.

Papillary lung carcinoma with prominent "morular" component.

Three cases of primary pulmonary papillary carcinomas with a prominent "morular" component involved 2 women and 1 man (age range, 25-68 years). The patients had symptoms related to the pulmonary mass, including chest pain, cough, and dyspnea. Radiographic evaluation of the thorax revealed the presence of a pulmonary mass. Surgical biopsies were obtained and reported as non-small cell carcinoma. All patients underwent lobectomy. Two tumors were located in the right upper lobe and 1 in the left upper lobe. The tumors were soft, white to tan, without evidence of necrosis or hemorrhage, and 2.5 to 3.5 cm in greatest diameter. The tumors were characterized predominantly by papillary architecture containing numerous "morules" composed of spindle cells without nuclear atypia or mitotic activity. Some morules were floating freely within papillary spaces; others seemed to detach from the papillary structures. Immunohistochemical studies of 2 tumors showed positivity for thyroid transcription factor-1, keratin, and carcinoembryonic antigen and negativity for thyroglobulin. The morules showed positive thyroid transcription factor-1 staining, weak keratin staining, and negative staining for smooth muscle actin, desmin, and HMB-45. These cases highlight an unusual phenomenon, that of primary papillary carcinomas of the lung with a prominent morular component.

Cribriform-Morular Variant of Papillary Carcinoma: Association with Familial Adenomatous Polyposis - Report of Three Cases and Review of Literature.

We describe a rare variant of papillary thyroid carcinoma (PTC), the Cribriform-Morular Variant (C-MV). A handful of cases have been described in the literature of this entity. They exhibit the morphologic features of a distinctive papillary neoplasm along with solid, cribriform, and squamoid-morular areas. The cribriform and morular features make this a separate entity which could be mistaken for a high grade aggressive thyroid neoplasm. These lesions are usually associated with familial adenomatosis polyposis (FAP) but rarely may be sporadic. We report three cases that we have encountered.

Placental transmogrification of the lung is a histologic pattern frequently associated with pulmonary fibrochondromatous hamartoma.

CONTEXT: Placental transmogrification of the lung is a term introduced to describe a peculiar histologic pattern characterized by formation of placental villuslike structures in the lung parenchyma. It has been reported to occur in association with bullous emphysema and lipomatosis. OBJECTIVES: To study the relationship between placental transmogrification and pulmonary hamartomas. DESIGN AND METHODS: Reports of 38 cases of pulmonary hamartomas during 18 years (1982-1999) were reviewed. All histologic slides of these cases were examined for the presence of villuslike papillary projections and placenta-like structures. Hamartomas with prominent papillary projections or placenta-like structures were further investigated to assess the histogenesis and proliferation of epithelial and stromal cells. Immunohistochemical analysis was performed on paraffin-embedded tissue using monoclonal antibodies against Ki-67 and thyroid transcription factor 1 (TTF-1) and polyclonal antibodies against c-Kit antigen (a stem cell factor receptor/mast cell growth factor receptor) in conjunction with Leder stain for naphthol-ASD-chloroacetate esterase. RESULTS: Placental transmogrification was identified in 6 of 38 cases of pulmonary fibrochondromatous hamartomas. The histologic change consisted of an abundant myxoid or edematous fibroadipose stroma with a respiratory epithelial lining, resulting in papillary projections that resembled immature placental villi. Epithelium lining the papillary projections was positive for TTF-1 (70%-90%) and Ki-67 (3%-5%). In contrast, stromal cells were negative for TTF-1 with only rare cells immunoreactive for Ki-67. A number of stromal spindle cells and occasional cells in epithelium were c-Kit immunoreactive; however, concurrent Leder stain demonstrated that these c-Kit-positive cells were mast cells and not stem cells. CONCLUSIONS: Placental transmogrification is frequently associated with pulmonary fibrochondromatous hamartomas and may be induced by or associated with a proliferation of lining epithelial components in the hamartomas. The significance of numerous mast cells within stroma of placental transmogrification is unclear and their possible role in inducing stromal proliferation needs to be further evaluated.

Clonality of combined tumors.

CONTEXT: Tumors with mixed morphologic patterns (combined tumors) are sometimes encountered, and questions often arise regarding the mechanism of molecular pathogenesis of each component and their relationships. OBJECTIVE: To determine whether different components of combined tumors contain the same or different genetic alterations, thus providing evidence for their clonality. MATERIALS AND METHODS: Six combined tumors with 2 components (in each case, both components showed epithelial differentiation morphologically) were studied by microdissecting tumor cells from each morphologic area followed by loss of heterozygosity analysis. RESULTS: In 1 of the cases studied, the different morphologic areas contained different patterns of genetic alterations. In the remaining 5 cases, the different morphologic areas harbored identical genetic changes in the chromosome regions studied. The latter group, interestingly, included a colonic tumor with an area of tubulovillous adenoma and an area of neuroendocrine carcinoma, and 2 lung tumors with squamous carcinoma and small cell carcinoma components. CONCLUSIONS: Our results suggest that in the majority of combined tumors, cells with different phenotypes share similar genotype and may arise from a single precursor cell. However, in a minority of these tumors, different areas may be derived from different precursor cells.

Lung adenocarcinoma biomarker incidence in Hispanic versus non-Hispanic white patients.

CONTEXT: Lung cancer is the leading cause of cancer deaths in the United States and worldwide. Biomarker testing is critical to personalized therapy in lung adenocarcinoma and has been extensively investigated in non-Hispanic whites, Asians, and African Americans. However, little information addresses the underlying genetic changes in lung adenocarcinoma among Hispanic patients in the United States. OBJECTIVE: To identify targetable biomarkers other than EGFR and EML4-ALK in Hispanic patients with lung adenocarcinoma. DESIGN: We tested DNA extracted from 85 lung adenocarcinoma specimens collected from 40 Hispanic and 43 non-Hispanic white patients for previously reported mutations in KRAS, MET, BRAF, mTOR, STAT3, JAK2, PIK3CA, AKT1 through AKT3, and PTEN with a custom Sequenom massARRAY assay (Sequenom, San Diego, California). RESULTS: Mutations in KRAS were identified in 11 cases (13%; 6 Hispanic [7%], 5 non-Hispanic white [6%]) and had no correlation with sex, age, or smoking history. Mutations in PIK3CA were identified in 2 of the 40 Hispanic patients (5%), including one patient (2.5%) with a concurrent KRAS mutation. The tumors were wild type for all other genes tested. CONCLUSIONS: Targetable biomarkers other than EGFR and EML4-ALK were identified in 7 of the 40 Hispanic patients (18%) and 5 of the 43 non-Hispanic white patients (12%), suggesting a similar mutational frequency. Our highly multiplexed genotyping assay detected actionable mutations in 14% (12 of 83) more patients than would have been identified by EGFR and EML4-ALK testing alone.