The Utility of Pathology Reports to Identify Persons With Cancer Recurrence.

BACKGROUND: Cancer recurrence is an important measure of the impact of cancer treatment. However, no population-based data on recurrence are available. Pathology reports could potentially identify cancer recurrences. Their utility to capture recurrences is unknown. OBJECTIVE: This analysis assesses the sensitivity of pathology reports to identify patients with cancer recurrence and the stage at recurrence. SUBJECTS: The study includes patients with recurrent breast (n=214) or colorectal (n=203) cancers. RESEARCH DESIGN: This retrospective analysis included patients from a population-based cancer registry who were part of the Patient-Centered Outcomes Research (PCOR) Study, a project that followed cancer patients in-depth for 5 years after diagnosis to identify recurrences. MEASURES: Information abstracted from pathology reports for patients with recurrence was compared with their PCOR data (gold standard) to determine what percent had a pathology report at the time of recurrence, the sensitivity of text in the report to identify recurrence, and if the stage at recurrence could be determined from the pathology report. RESULTS: One half of cancer patients had a pathology report near the time of recurrence. For patients with a pathology report, the report's sensitivity to identify recurrence was 98.1% for breast cancer cases and 95.7% for colorectal cancer cases. The specific stage at recurrence from the pathology report had a moderate agreement with gold-standard data. CONCLUSIONS: Pathology reports alone cannot measure population-based recurrence of solid cancers but can identify specific cohorts of recurrent cancer patients. As electronic submission of pathology reports increases, these reports may identify specific recurrent patients in near real-time.

Neutrophilic inflammation in gallbladder carcinoma correlates with patient survival: A case-control study.

Gallbladder carcinoma is an uncommon malignancy with an overall 5-year survival of less than 5%. Gallbladder carcinoma has been strongly linked with cholelithiasis and chronic inflammation. Case reports and series have described cholecystitis with acute (neutrophilic) inflammation in association with gallbladder carcinoma, although a clear relationship to patient outcome has not been established. Our series included 8 cases of gallbladder carcinoma with high tumor-associated neutrophils (>25 per high power field) that were associated with shorter patient survival (Cox regression coefficient 6.2, p = 0.004) than age- and stage-matched controls. High tumor-associated neutrophils were not associated with gallbladder rupture/perforation or increased bacterial load measured by 16S PCR. Neutrophilic inflammation with gallbladder carcinoma correlates to shorter survival, independent of patient age and stage of carcinoma. The findings suggest that the degree of neutrophilic inflammation may have prognostic significance in specimens from patients with gallbladder carcinoma after cholecystectomy. Further studies with larger case numbers are needed to confirm and generalize these findings.

Prevalence, risk factors, and surveillance patterns for gastric intestinal metaplasia among patients undergoing upper endoscopy with biopsy.

BACKGROUND AND AIMS: Gastric intestinal metaplasia (GIM) is an important precursor lesion to gastric cancer (GC), the second leading cause of cancer death worldwide. There exist few data regarding the prevalence of, risk factors for, and clinical practice patterns regarding GIM in the United States. Furthermore, there are currently no U.S. guidelines regarding screening/surveillance for GIM. METHODS: All consecutive upper endoscopic procedures from 2 academic medical centers in Seattle between 1999 and 2014 were reviewed. Demographic, clinical, and endoscopic covariates were recorded at time of endoscopy. Procedures with gastric biopsy were matched to final the histologic diagnoses, including the presence of Helicobacter pylori. Cases of GIM and dysplasia were recorded and compared with non-GIM controls using univariate and multivariable regression. Surveillance patterns for cases of GIM were recorded. RESULTS: Data from 36,799 upper endoscopies, 17,710 gastric biopsies, 2073 cases of GIM, 43 cases of dysplasia, and 78 cases of GC were captured. The point prevalence of GIM was 11.7% in patients who underwent gastric biopsy. Non-white race (P < .001), increasing age (P < .001), and presence of H pylori (P < .001) were associated with GIM. If GIM was present, increasing age (P < .001) and male gender (P < .001) were associated with progression, and the presence of H pylori (P < .001) was inversely associated with progression to dysplasia/GC. Few cases of GIM/dysplasia/GC were identified during procedures for GIM screening/surveillance. Only 16% of patients with a diagnosis of GIM received a recommendation for surveillance. CONCLUSIONS: There is a high prevalence of GIM among non-white and Hispanic Americans. Risk factors for development of GIM may be distinct from the risk factors for progression to GC.

Association of gastric intestinal metaplasia and East Asian ethnicity with the risk of gastric adenocarcinoma in a U.S. population.

BACKGROUND AND AIMS: Although the incidence of gastric cancer is higher than that of esophageal cancer in the United States, no screening or surveillance guidelines exist. The aim of this study is to evaluate the association between gastric intestinal metaplasia and the risk of gastric cancer in a U.S. tertiary care system with a large immigrant population. METHODS: This is a retrospective case-control study with cases of biopsy-proven gastric cancer matched (by age and gender) to controls without gastric cancer who had undergone EGD. The presence of gastric intestinal metaplasia was ascertained from pathology reports. Other potential risk factors for gastric cancer were abstracted from medical records as follows: country of origin, Helicobacter pylori infection, family history of gastric cancer, alcohol consumption, smoking, and history of partial gastrectomy (Billroth I or II). Conditional logistic regression was used to identify independent risk factors for gastric cancer. RESULTS: One hundred fifty-two cases of gastric cancer were compared with 456 age- and gender-matched controls. The mean age was 66 years, and 57% were male. Multivariable analysis identified 2 significant predictors of gastric cancer: the presence of gastric intestinal metaplasia (odds ratio [OR], 9.3; 95% confidence interval [CI], 4.5-18.9; P < .001) and East Asian ethnicity (OR, 15.9; 95% CI, 5.8-43.6; P < .001). CONCLUSION: The presence of gastric intestinal metaplasia on endoscopy and East Asian ethnicity were significant risk factors for gastric cancer. Screening East Asian immigrants and surveying patients with gastric intestinal metaplasia may improve the rates of early detection of gastric cancer in the United States.

Interstitial Lung Disease in India. Results of a Prospective Registry.

RATIONALE: Interstitial lung disease (ILD) is a heterogeneous group of acute and chronic inflammatory and fibrotic lung diseases. Existing ILD registries have had variable findings. Little is known about the clinical profile of ILDs in India. OBJECTIVES: To characterize new-onset ILDs in India by creating a prospective ILD using multidisciplinary discussion (MDD) to validate diagnoses. METHODS: Adult patients of Indian origin living in India with new-onset ILD (27 centers, 19 Indian cities, March 2012-June 2015) without malignancy or infection were included. All had connective tissue disease (CTD) serologies, spirometry, and high-resolution computed tomography chest. ILD pattern was defined by high-resolution computed tomography images. Three groups independently made diagnoses after review of clinical data including that from prompted case report forms: local site investigators, ILD experts at the National Data Coordinating Center (NDCC; Jaipur, India) with MDD, and experienced ILD experts at the Center for ILD (CILD; Seattle, WA) with MDD. Cohen's κ was used to assess reliability of interobserver agreement. MEASUREMENTS AND MAIN RESULTS: A total of 1,084 patients were recruited. Final diagnosis: hypersensitivity pneumonitis in 47.3% (n = 513; exposure, 48.1% air coolers), CTD-ILD in 13.9%, and idiopathic pulmonary fibrosis in 13.7%. Cohen's κ: 0.351 site investigator/CILD, 0.519 site investigator/NDCC, and 0.618 NDCC/CILD. CONCLUSIONS: Hypersensitivity pneumonitis was the most common new-onset ILD in India, followed by CTD-ILD and idiopathic pulmonary fibrosis; diagnoses varied between site investigators and CILD experts, emphasizing the value of MDD in ILD diagnosis. Prompted case report forms including environmental exposures in prospective registries will likely provide further insight into the etiology and management of ILD worldwide.

Gallbladder carcinoma and epithelial dysplasia: Appropriate sampling for histopathology.

Gallbladder carcinoma (GC) is an uncommon malignancy with an overall 5-year survival of <5%. Due to overlap of clinical presentation with the more common cholecystitis, an estimated 50-65% of all GCs are found incidentally. Epithelial dysplasia is identified in ~50% of specimens with invasive carcinoma. Recent expert panel guidelines have recommended histologic examination of the entire gallbladder in cases where initial sampling reveals dysplasia. 89 cases of GC, 34 high grade dysplasia (HGD), and 60 low grade dysplasia (LGD) were identified in cholecystectomy specimens assessed at our institution over the last 15 years. Pre-operative imaging (either ultrasound or CT) only identified 52% of mass lesions in GC cases. Among gallbladder specimens with epithelial dysplasia only at initial sampling, additional sectioning was performed in 59% of HGD and 55% of LGD. Additional sectioning of gallbladder specimens with HGD had a higher yield (10%) for identifying invasive carcinoma than those with LGD (0 of 28). The diagnostic yield of additional sectioning is significantly higher in the setting of high grade as compared to low grade dysplasia, suggesting that sampling at the discretion of the pathologist may be sufficient for the latter.

'Non-classical' HER2 FISH results in breast cancer: a multi-institutional study.

The 2013 CAP/ASCO HER2 Testing Guidelines Update modified HER2 FISH categories such that some cases with 'monosomy', 'co-amplification/polysomy', low-level increased HER2 signals or clustered heterogeneity now are considered amplified or equivocal. This study examines the frequency and clinico-pathologic characteristics of breast cancers with equivocal or 'non-classical' HER2 FISH results. Breast cancers (2001-2014) with HER2 FISH results, HER2 immunohistochemistry, ER, grade, and age from three institutions (Stanford, UCSF, UWMC) were collected. HER2 FISH was interpreted using the updated recommendations. Amplified cases with non-classical results were grouped into the following categories: (1) 'monosomy' (ratio ≥2.0, mean HER2/cell<4.0); (2) 'co-amplified' (ratio<2.0, mean HER2/cell ≥6.0); (3) 'low amplified' (ratio ≥2.0, mean HER2/cell 4.0-5.9). Heterogeneous cases with clustered HER2-positive cells were also included. Of 8068 cases, 5.2% were equivocal and 4.6% had a 'non-classical' HER2 amplified result; 1.4% 'monosomy', 0.8% 'co-amplified', 2.1% 'low amplified', and 0.3% clustered heterogeneity. These cancers had a high frequency of ER positive (80.4%), Nottingham grade 3 (52.1%) results. The highest percentage of grade 3 cancers (66.7%) and positive HER2 immunohistochemistry (31.7%) was in the 'co-amplified' group. The 'monosomy' group had the highest percent grade 1 cancers (13.3%) and was most frequently HER2 immunohistochemistry negative (30.1%). Equivocal cases had very similar characteristics to the 'low-amplified' category. Cases with non-classical HER2 amplification or equivocal results are typically ER positive, higher grade cancers. 'Co-amplified' cases have the highest frequencies of aggressive characteristics and 'monosomy' cases the highest frequencies of lower risk features. With little clinical outcomes data currently available on these non-classical HER2 results, these results support the current classification scheme for HER2 FISH, with case-by-case correlation with additional clinical-pathologic factors when evaluating whether to offer HER2-targeted therapies in these non-classical cases.

A Distributed Network for Intensive Longitudinal Monitoring in Metastatic Triple-Negative Breast Cancer.

Accelerating cancer research is expected to require new types of clinical trials. This report describes the Intensive Trial of OMics in Cancer (ITOMIC) and a participant with triple-negative breast cancer metastatic to bone, who had markedly elevated circulating tumor cells (CTCs) that were monitored 48 times over 9 months. A total of 32 researchers from 14 institutions were engaged in the patient's evaluation; 20 researchers had no prior involvement in patient care and 18 were recruited specifically for this patient. Whole-exome sequencing of 3 bone marrow samples demonstrated a novel ROS1 variant that was estimated to be present in most or all tumor cells. After an initial response to cisplatin, a hypothesis of crizotinib sensitivity was disproven. Leukapheresis followed by partial CTC enrichment allowed for the development of a differential high-throughput drug screen and demonstrated sensitivity to investigational BH3-mimetic inhibitors of BCL-2 that could not be tested in the patient because requests to the pharmaceutical sponsors were denied. The number and size of CTC clusters correlated with clinical status and eventually death. Focusing the expertise of a distributed network of investigators on an intensively monitored patient with cancer can generate high-resolution views of the natural history of cancer and suggest new opportunities for therapy. Optimization requires access to investigational drugs.

Histiocytic disorders of the chest: imaging findings.

Histiocytic disorders of the chest comprise a broad spectrum of diseases. The lungs may be involved in isolation or as part of systemic disease. Some of these disorders are primary and have unknown etiology, and others result from a histiocytic response to a known cause. Among primary histiocytic disorders, pulmonary Langerhans cell histiocytosis (PLCH) is the most common; others include Erdheim-Chester disease and Rosai-Dorfman disease. Adult PLCH occurs almost exclusively in adults aged 20-40 years who smoke. Pediatric PLCH is extremely rare and typically occurs as part of multisystemic disease. Erdheim-Chester disease affects middle-aged and older adults; thoracic involvement usually occurs as part of systemic disease. Rosai-Dorfman disease affects children and young adults and manifests as painless cervical lymphadenopathy. Examples of secondary histiocytic disorders are storage diseases such as Gaucher disease, Niemann-Pick disease, and Fabry disease; pneumoconiosis such as silicosis and coal workers' pneumoconiosis; and infections such as Whipple disease and malakoplakia. These disorders are characterized at histopathologic examination on the basis of infiltration of alveoli or the pulmonary interstitium by histiocytes, which are a group of cells that includes macrophages and dendritic cells. Dendritic cells are a heterogeneous group of nonphagocytic antigen-presenting immune cells. Immunohistochemical markers help to distinguish among various primary histiocytic disorders. Characteristic radiologic findings in the appropriate clinical context may obviate biopsy to establish a correct diagnosis. However, in the absence of these findings, integration of clinical, pathologic, and radiologic features is required to establish a diagnosis.

Pulmonary effects of i.v. injection of crushed oral tablets: "excipient lung disease".

OBJECTIVE: When crushed oral tablets are injected i.v., their filler material (excipient) can induce a potentially fatal foreign-body reaction in pulmonary arterioles, presenting as dyspnea and pulmonary hypertension with centrilobular nodules on CT. We will describe the imaging and pathologic features of "excipient lung disease." CONCLUSION: The radiologist has a critical role in recognizing and reporting excipient lung disease because the referring clinician may be unaware of the patient's i.v. drug abuse.

Tumorlike conditions of the pleura.

Tumorlike conditions of the pleura are rare, but diagnosis is facilitated by recognizing certain imaging patterns and interpreting them in the clinical context. A tumorlike condition of the pleura is any nonneoplastic lesion of the pleura itself, or within the pleural space, that resembles a tumor. An approach to diagnosis of the tumorlike conditions of the pleura is provided, and these conditions are grouped into focal or diffuse conditions, with an emphasis on specific imaging features. Focal tumorlike conditions of the pleura include pleural plaque, thoracic splenosis, thoracic endometriosis causing catamenial pneumothorax, and pseudotumor caused by pleural effusion. Thoracic splenosis should be considered in a patient who has a healed left lower rib fracture, an absent spleen, and left lower pleural nodules. Thoracic endometriosis with catamenial pneumothorax should be considered in a woman of childbearing age who presents with right scapular pain and recurrent pneumothorax occurring at or around the onset of menses. Extrapleural hematoma is a nonpleural mimic of pleural tumor and shares some imaging features with focal tumorlike conditions of the pleura, despite residing in the extrapleural space. Diffuse tumorlike conditions of the pleura include diffuse pleural thickening and rare conditions such as Erdheim-Chester disease and diffuse pulmonary lymphangiomatosis. Erdheim-Chester disease should be considered when diffuse pleural thickening occurs with a perirenal soft-tissue halo or distal femoral sclerosis. Diffuse pulmonary lymphangiomatosis should be considered when findings include diffuse pleural thickening, interlobular septal and peribronchovascular interstitial thickening, and mediastinal fat infiltration limited to the thorax and when these findings persist despite diuretic therapy.

Patient and physician perceptions about blood transfusions in the myelodysplastic syndromes.

BACKGROUND: Little is known about the shared decision-making between patients with transfusion-dependent (TD) myelodysplastic syndromes (MDS) and their physicians about the benefits, risks, and alternatives to reduce the need for blood transfusions. METHODS AND MATERIALS: We conducted interviews and two cross-sectional surveys of MDS patients and MDS physicians in the US about the use of blood transfusions and disease-modifying therapies (DMTs). Responses from 157 MDS patients and 109 MDS physicians were analyzed. RESULTS: The TD-MDS patient cohort had a median age of 69 years and a greater proportion of lower IPSS risk. The MDS physicians primarily practiced in large centers, evenly distributed between academic and community hospitals. There was a high level of independence and generally positive quality of life among patients, who were mostly concerned about effectiveness of blood transfusions and iron overload. MDS patients with shorter duration of disease (less than 5 years) were primarily concerned with transfusion reaction, while MDS patients with longer duration of disease were primarily concerned with iron overload. Approximately half of TD-MDS patients stated they had not discussed alternatives to reduce the need for blood transfusions with their physician. Patients with longer duration of disease were more likely to have a discussion with their physician about alternatives to blood transfusions. Physicians stated that they administered blood transfusions as primary therapy for MDS when it was patient preference, advanced age of patient, frailty, lower risk MDS, significant comorbidities, or failed prior treatments. CONCLUSIONS: While quality of life seemed generally positive in TD-MDS patients, there were differing perceptions about blood transfusions between patients and physicians. In the future, appraisal and optimization of the informed consent process between MDS patients and physicians are needed.

Serology Is More Sensitive Than Urea Breath Test or Stool Antigen for the Initial Diagnosis of Helicobacter pylori Gastritis When Compared With Histopathology.

OBJECTIVES: To assess the concordance and performance characteristics of Helicobacter pylori laboratory tests compared with histopathology and to propose algorithms for the diagnosis of H pylori that minimize diagnostic error. METHODS: H pylori diagnostics were reviewed from a 12-year period within a health system (2,560 cases). Analyses were performed to adjust diagnostic performance based on treatment and consensus histopathologic diagnoses among pathologists. Markers of access to care, including test cancellation frequency and turnaround time, were assessed. Costs and performance of candidate noninvasive testing algorithms were modeled as a function of disease prevalence. RESULTS: Serum H pylori IgG demonstrated a higher sensitivity (0.94) than urea breath and stool antigen tests (0.64 and 0.61, respectively). Evidence of an advantage in access to care for serology included a lower cancellation rate. Interobserver variability was higher (κ = 0.34) among pathologists for cases with a discordant laboratory test than concordant cases (κ = 0.56). A model testing algorithm utilizing serology for first-time diagnoses minimizes diagnostic error. CONCLUSIONS: Although H pylori serology has modestly lower specificity than other noninvasive tests, the superior sensitivity and negative predictive value in our population support its use as a noninvasive test to rule out H pylori infection. Reflexive testing with positive serology followed by either stool antigen or urea breath test may optimize diagnostic accuracy in low-prevalence populations.

A multi-institutional review of outcomes in biopsy-proven chronic invasive fungal sinusitis.

BACKGROUND: Chronic invasive fungal sinusitis (CIFS) is a rare, life-threatening infection of the nose and sinuses. This study aims to identify factors that impact survival in 1 of the largest cohorts to date. METHODS: Pathology records were reviewed for biopsy-proven CIFS from 3 tertiary academic institutions from 1995 to 2016. Variables were analyzed using log-rank survival analysis. Univariate Cox regression was performed at 1 and 12 months. RESULTS: Thirty-eight patients were included. Hematologic malignancy and diabetes were the most common underlying diseases (32% each). Aspergillus was the most common fungus (63%). Greater than 75% of the patients had an absolute neutrophil count (ANC) >1000 at the time of diagnosis. Overall survival at 1, 6, and 12 months was 89%, 68%, and 48%, respectively. In univariate analysis, factors associated with worse survival included: ANC <500 at 12 months (hazard ratio [HR] 4.8; p = 0.01), ANC <1000 at 12 months (HR 5.8; p = 0.001), and recent chemotherapy (HR 4; p = 0.01). The following factor was associated with improved survival in univariate analysis: ANC as a linear variable in the entire cohort (HR 0.7; p = 0.005). CONCLUSION: We present a multi-institutional case-series of CIFS and long-term follow-up. ANC <1000 at time of diagnosis and recent chemotherapy (within 1 month of diagnosis) are associated with poorer survival, whereas a rising ANC >1000 is associated with improved survival at 12 months. Further prospective studies are needed to further define factors that affect outcomes.

Imaging of thoracic lymphatic diseases.

OBJECTIVE: This review will focus on radiographic description of lymphangiomas, lymphangiohemangiomas, pulmonary lymphangiomatosis, lymphangiectasis, lymphangioleiomyomatosis, lymphatic dysplasia, and traumatic lymphatic injury. CONCLUSION: Diseases of the thoracic lymphatic system have a wide variety of unique radiographic manifestations, all of which can be explained by the underlying pathophysiology and relationship to the normal distribution of lymphatics in the chest.

18F FDG-PET/CT findings in recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is an indolent and primary disease of the larynx and the trachea and rarely extends to smaller airways. F-18 fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT) evaluation in this condition has not been reported earlier. We report FDG-PET/CT findings in a case of RRP that included a large papillomatous lung mass resembling cancer.

Regional lymph node sampling in lung carcinoma: a single institutional and national database comparison.

Assessing regional lymph node metastasis is a key component of lung carcinoma staging and prognostication. Recent guidelines have suggested a quality metric of 10 total regional lymph nodes sampled with each stage I-II primary lung carcinoma resection. However, the extent of mediastinal lymph node sampling remains controversial. We assessed factors contributing to regional lymph node counts and effect on overall patient survival in an institutional cohort of 888 cases and the Surveillance, Epidemiology, and End Results national cancer registry (10 856 cases). The distribution of total lymph node counts in lobectomy and pneumonectomy cases was variable with a median of 10 and an interquartile range of 7 to 14. Multiple clinical and pathologic factors correlated with total regional node counts. Total lymph node counts of at least 10 in the institutional cohort did not correlate with significant differences in overall survival as compared with node counts of less than 10 (P = .38). In the Surveillance, Epidemiology, and End Results database, although 0 regional lymph nodes were correlated with reduced overall survival (hazard ratio, 1.47; P < .01), no significant difference was detected for 1 to 9 versus at least 10 nodes (P = .8). In conclusion, lymph node counts for primary lung carcinoma are driven by surgical, pathologic, and biologic variability. We find no evidence for a meaningful quality metric of 10 total regional lymph nodes at the institutional and national registry levels.

A multi-institutional review of outcomes in biopsy-proven acute invasive fungal sinusitis.

BACKGROUND: Acute invasive fungal sinusitis (AIFS) is a rare, aggressive infection occurring in immunocompromised patients. In this study we examined factors that affect survival in AIFS, and whether immune-stimulating therapies (IST) improve survival. METHODS: Pathology records of biopsy-proven AIFS were reviewed from 3 academic institutions from 1995 to 2016. Univariate and multivariate Cox regressions were performed at 1 and 3 months from diagnosis. RESULTS: One hundred fourteen patients were included; 45 received IST. In the univariate analysis, the following factors were associated with worse survival: hematologic malignancy (3-month hazard ratio [HR], 3.7; p = 0.01); recent chemotherapy (within 1 month of AIFS diagnosis) (3-month HR, 2.3; p = 0.02); recent bone marrow transplant (BMT) (3-month HR, 2.5; p = 0.02); and infection with atypical fungi (1-month HR, 3.1; p = 0.04). The following were associated with improved survival in univariate analysis: increasing A1c% (1-month HR, 0.7; p = 0.01) and surgical debridement (1-month HR, 0.1; p = 0.001). One third of patients with a hematologic malignancy had an absolute neutrophil count (ANC) >1000 at the time of diagnosis. ANC was not associated with prognosis in these patients. The following were associated with worse survival in multivariate analyses: hematologic malignancy; recent chemotherapy; atypical organisms; and cavernous sinus extension. In multivariate analyses, IST was associated with a 70% reduction in mortality at 1 month (p = 0.02). CONCLUSION: We presented the largest series of AIFS. Further studies are needed to examine the importance of ANC in diagnosis and prognosis. Patients diagnosed with atypical organisms may be at higher risk of death. IST likely improves short-term survival, but prospective studies are needed.