Fine particle air pollution and lung cancer risk: Extending the long list of health risks.

Exposures to fine particulate matter (PM2.5) concentrations above the WHO guidelines affect 99% of the world population. In a recent issue of Nature, Hill et al. dissect the tumor promotion paradigm orchestrated by PM2.5 inhalation exposures in lung carcinogenesis, supporting the hypothesis that PM2.5 can increase your risk of lung carcinoma without ever smoking.

Case of recurrent superficial CD34-positive fibroblastic tumor.

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently described rare superficial mesenchymal tumor. SCPFT has a distinctive morphologic appearance, marked by significant nuclear pleomorphism, low mitotic rate, and diffuse CD34 positivity. SCPFT is underdiagnosed because of its rarity and misdiagnosis as sarcoma, with very few reported cases of local recurrence or metastasis. Recognition and awareness of SCPFT are essential for accurate diagnosis and appropriate clinical management. We describe here the case of a 37-year-old male who presented with a right calf mass diagnosed as SCPFT with subsequent local recurrence of the tumor.

Air Pollution, Ultrafine Particles, and Your Brain: Are Combustion Nanoparticle Emissions and Engineered Nanoparticles Causing Preventable Fatal Neurodegenerative Diseases and Common Neuropsychiatric Outcomes?

Exposure to particulate matter (PM) pollution damages the human brain. Fossil fuel burning for transportation energy accounts for a significant fraction of urban air and climate pollution. While current United States (US) standards limit PM ambient concentrations and emissions, they do not regulate explicitly ultrafine particles (UFP ≤ 100 nm in diameter). There is a growing body of evidence suggesting UFP may play a bigger role inflicting adverse health impacts than has been recognized, and in this perspective, we highlight effects on the brain, particularly of young individuals. UFP penetrate the body through nasal/olfactory, respiratory, gastrointestinal, placenta, and brain-blood barriers, translocating in the bloodstream and reaching the glymphatic and central nervous systems. We discuss one case study. The 21.8 million residents in the Metropolitan Mexico City (MMC) are regularly exposed to fine PM (PM2.5) above the US 12 µg/m3 annual average standards. Alzheimer's disease (AD), Parkinson's disease (PD), and TAR DNA-binding protein (TDP-43) pathologies and nanoparticles (NP ≤ 50 nm in diameter) in critical brain organelles have been documented in MMC children and young adult autopsies. MMC young residents have cognitive and olfaction deficits, altered gait and equilibrium, brainstem auditory evoked potentials, and sleep disorders. Higher risk of AD and vascular dementia associated with residency close to high traffic roadways have been documented. The US is not ready or prepared to adopt ambient air quality or emission standards for UFP and will continue to focus regulations only on the total mass of PM2.5 and PM10. Thus, this approach raises the question: are we dropping the ball? As research continues to answer the remaining questions about UFP sources, exposures, impacts, and controls, the precautionary principle should call us to accelerate and expand policy interventions to abate or eliminate UFP emissions and to mitigate UFP exposures. For residents of highly polluted cities, particularly in the developing world where there is likely older and dirtier vehicles, equipment, and fuels in use and less regulatory oversight, we should embark in a strong campaign to raise public awareness of the associations between high PM pollution, heavy traffic, UFP, NP, and neuropsychiatric outcomes, including dementia. Neurodegenerative diseases evolving from childhood in polluted, anthropogenic, and industrial environments ought to be preventable.

Superficial CD34-positive fibroblastic tumor (SCPFT): A review of pathological and clinical features.

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently described rare mesenchymal tumor of borderline malignancy. It generally involves superficial soft tissue, with a predilection to the lower extremities. Microscopically this tumor is characterized by a fascicular and storiform growth pattern, spindled to epithelioid cells, nuclear atypia with pleomorphism, and eosinophilic granular, and fibrillar to glassy cytoplasm. Strong diffuse immunoreactivity for CD34 is very characteristic of this entity. Due to under-recognition, this tumor is generally underreported. Additionally, cases of recurrence are rarely reported in the literature. We will comprehensively review the English language literature on all reported cases of SCPFT, with emphasis on recurrence.

Enhanced Succinate Oxidation with Mitochondrial Complex II Reactive Oxygen Species Generation in Human Prostate Cancer.

The transformation of prostatic epithelial cells to prostate cancer (PCa) has been characterized as a transition from citrate secretion to citrate oxidation, from which one would anticipate enhanced mitochondrial complex I (CI) respiratory flux. Molecular mechanisms for this transformation are attributed to declining mitochondrial zinc concentrations. The unique metabolic properties of PCa cells have become a hot research area. Several publications have provided indirect evidence based on investigations using pre-clinical models, established cell lines, and fixed or frozen tissue bank samples. However, confirmatory respiratory analysis on fresh human tissue has been hampered by multiple difficulties. Thus, few mitochondrial respiratory assessments of freshly procured human PCa tissue have been published on this question. Our objective is to document relative mitochondrial CI and complex II (CII) convergent electron flow to the Q-junction and to identify electron transport system (ETS) alterations in fresh PCa tissue. The results document a CII succinate: quinone oxidoreductase (SQR) dominant succinate oxidative flux model in the fresh non-malignant prostate tissue, which is enhanced in malignant tissue. CI NADH: ubiquinone oxidoreductase activity is impaired rather than predominant in high-grade malignant fresh prostate tissue. Given these novel findings, succinate and CII are promising targets for treating and preventing PCa.

Leiomyoma of digit of hand: Report of three cases with literature review.

Leiomyoma is a benign tumor of smooth muscle origin most common in areas of the body with abundant smooth muscle including the gynecologic, genitourinary, and gastrointestinal system. Leiomyoma outside of these locations is believed to arise from vascular smooth muscle and arrector pili muscles. Leiomyoma of an extremity is a rare diagnosis, especially when present in a digit of the hand due to the paucity of smooth muscle in this location. We report three cases of leiomyoma of a digit of the hand.

Pleomorphic giant cell carcinoma of prostate: Rare tumor with unique clinicopathological, immunohistochemical, and molecular features.

Pleomorphic giant cell carcinoma (PGCC) of the prostate is a rare entity categorized as a variant of prostatic acinar adenocarcinoma in the 2016 World Health Organization (WHO) classification system. PGCC differs from conventional prostatic adenocarcinoma by having bizarre, markedly enlarged, and pleomorphic cells. It differs from high grade urothelial carcinoma by negativity for urothelial differentiation markers, and can be distinguished from sarcomatoid carcinoma by lack of spindle cells. Including two new cases described herein, there have been 51 cases of prostate PGCC reported in the English literature. Clinical features shared by cases of prostate PGCC include poor prognosis, occurrence in older patients, and frequent association with prior therapy. Pathologic features common to cases of prostate PGCC include admixture with a high-grade conventional prostate carcinoma component and absent or reduced expression of prostate differentiation markers. More recent studies have begun to elucidate the molecular characteristics of PGCC, detecting specific mutations and chromosomal translocations, and showing evidence of a high degree of molecular instability in these tumors. We report novel findings in two cases of PGCC including a PIK3CA p.His1047Arg mutation not previously described. One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.

Seminal vesicle invasion combined with extraprostatic extension is associated with higher frequency of biochemical recurrence and lymph node metastasis than seminal vesicle invasion alone: Proposal for further pT3 prostate cancer subclassification.

The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system subdivides prostatic pT3 tumors into pT3a, which includes cases with extraprostatic extension (EPE) and pT3b, which is defined by the presence of seminal vesicle invasion (SVI) with or without EPE. Yet, it is not established whether combined SVI and EPE impart a worse prognosis compared to SVI alone. We studied a cohort of 69 prostatectomy patients with SVI with or without EPE. Patient age at the time of radical prostatectomy was documented and Gleason score and presence or absence of EPE and/or SVI were determined. Biochemical recurrence (BCR) was defined as a PSA rise >0.2 ng/mL. The frequency of BCR was 33.9% in cases with combined EPE and SVI versus 12.5% in cases with SVI alone (relative risk = 2.71). An additional cohort of 88 patients also showed a higher frequency of lymph node metastasis of 29% in patients with combined SVI and EPE at the time of radical prostatectomy versus a 10% frequency of lymph node metastasis in patients with SVI alone (relative risk = 2.9). Based on our data, we propose further subdividing pT3 prostate cancers into three groups: EPE alone (pT3a), SVI alone (pT3b), and combined EPE and SVI (pT3c). This classification system would more accurately identify patients with pT3 prostate cancer who are more likely to experience worse outcomes and provide clinicians with additional information to aid in follow-up and postoperative treatment decisions.

Clear cell carcinoma of testis: A review.

Clear cell Mullerian-type adenocarcinoma of the testis is an exceedingly rare entity, and its histogenesis and clinical behavior are still poorly understood. We discuss three cases of clear cell carcinoma of the testis, compiled from a review of the literature and our personal experience. Microscopically, the tumors closely resembled clear cell carcinoma of the ovary, displaying papillae lined by clear cells with areas of hobnailing. The reported immunophenotypic features were also similar to that of ovarian tumors, as positivity for epithelial markers (CK7, CAM5.2, AE1/AE3, EMA) and Mullerian markers (PAX8, CA125) with negativity for estrogen and progesterone receptors have been observed. The pathogenesis of testicular clear cell carcinoma is still poorly understood, with reported cases displaying evidence of both mesothelial and Mullerian origin. In addition, molecular characterization of testicular clear cell carcinomas has yet to be accomplished; however, studies performed on ovarian clear cell carcinomas may provide insight to the origin, biologic behavior, and potential therapeutic modalities for this obscure, aggressive malignancy.

Micropapillary adenocarcinoma of lung: Morphological criteria and diagnostic reproducibility among pulmonary pathologists.

CONTEXT: Invasive micropapillary adenocarcinoma (MPC) is an aggressive variant of lung adenocarcinoma, frequently manifesting with advanced stage lymph node metastasis and decreased survival. OBJECTIVE: Identification of this morphology is important, as it is strongly correlated with poor prognosis regardless of the amount of MPC component. To date, no study has investigated the morphological criteria used to objectively diagnose it. DESIGN: Herein, we selected 30 cases of potential MPC of lung, and distributed 2 digital images per case among 15 pulmonary pathology experts. Reviewers were requested to diagnostically interpret, assign the percentage of MPC component, and record the morphological features they identified. The noted features included: columnar cells, elongated slender cell nests, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial signet ring-like forms, intracytoplasmic vacuolization, multiple nests in the same alveolar space, back-to-back lacunar spaces, epithelial nest anastomosis, marked pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, small/medium/large tumor nest size, fibrovascular cores, and spread through air-spaces (STAS). RESULTS: Cluster analysis revealed three subgroups with the following diagnoses: "MPC", "combined papillary and MPC", and "others". The subgroups correlated with the reported median percentage of MPC. Intracytoplasmic vacuolization, epithelial nest anastomosis/confluence, multiple nests in the same alveolar space, and small/medium tumor nest size were the most common criteria identified in the cases diagnosed as MPC. Peripherally oriented nuclei and epithelial signet ring-like forms were frequently identified in both the "MPC" and "combined papillary and MPC" groups. CONCLUSIONS: Our study provides objective diagnostic criteria to diagnose MPC of lung.

Flat epithelial atypia in directional vacuum-assisted biopsy of breast microcalcifications: surgical excision may not be necessary.

The aim of this study was to analyze the clinicopathological features of patients with flat epithelial atypia, diagnosed in directional vacuum-assisted biopsy targeting microcalcifications, to identify upgrade rate to in situ ductal or invasive breast carcinoma, and determine factors predicting carcinoma in the subsequent excision. We retrospectively evaluated the histological, clinical, and mammographic features of 69 cases from 65 women, with directional vacuum-assisted biopsy-diagnosed flat epithelial atypia with or without atypical ductal hyperplasia or atypical lobular hyperplasia, which underwent subsequent surgical excision. The extent and percentage of microcalcifications sampled by directional vacuum-assisted biopsy were evaluated by mammography. All biopsy and surgical excision slides were reviewed. The age of the women ranged from 40 to 85 years (mean 57 years). All patients presented with mammographically detected microcalcifications only, except in one case that had associated architectural distortion. Extent of calcifications ranged from <1 cm (n = 47), 1-3 cm (n = 15) to > 3 cm (n = 6), and no measurement (n = 1). A mean of 11 cores (range 6-25) was obtained from each lesion. Post-biopsy mammogram revealed >90% removal of calcifications in 81% of cases. Pure flat epithelial atypia represented nearly two-thirds of directional vacuum-assisted biopsy specimens (n = 43, 62%), while flat epithelial atypia coexisted with atypical ductal hyperplasia (18 cases, 26%), or atypical lobular hyperplasia (8 cases, 12%). Upon excision, none of the cases were upgraded to in situ ductal or invasive breast cancer. In one case, however, an incidental, tubular carcinoma (4 mm) was found away from biopsy site. Excluding this case, the upgrade rate was 0%. Our study adds to the growing evidence that diagnosis of flat epithelial atypia on directional vacuum-assisted biopsy for microcalcifications as the only imaging finding is not associated with a significant upgrade to carcinoma on excision, and therefore, excision may not be necessary. Additionally, excision may not be necessary for flat epithelial atypia with atypical ductal hyperplasia limited to ≤2 terminal duct-lobular units, if at least 90% of calcifications have been removed on biopsy.

Clinical presentation of ductal carcinoma in situ of breast with intraluminal crystalloids: Radiologic-histologic correlation.

Intraluminal crystalloids have rarely been described in the breast, particularly in cases with ductal carcinoma in situ (DCIS). We recently encountered a case of DCIS of the breast associated with numerous intraluminal crystalloids. The patient presented with a mass in the right breast, and microcalcifications were detected on screening and diagnostic mammograms; the patient underwent needle biopsies, lumpectomy, and skin-sparing mastectomy. Invasive ductal carcinoma associated with extensive DCIS was diagnosed. Multiple refractile, eosinophilic crystalloids, with variable morphologies including rectangular, triangular and needle-like with sharp borders, were observed within the lumina of DCIS, besides calcium phosphate microcalcifications. We report this case together with a literature review on crystalloid-containing lesions in breast and non-breast tissues. We also studied radiologic findings of these crystalloids using a specimen radiograph.

Primary collision tumors of the kidney composed of oncocytoma and papillary renal cell carcinoma: A review.

BACKGROUND: There are well known cases of hybrid tumors of chromophobe renal cell carcinoma (RCC) and oncocytoma in kidney, where both tumors have the same cell of origin - intercalated cell of the collecting duct. However, collision tumors composed of neoplasms originating from different cell lineages such as oncocytoma and papillary RCC are extremely rare. Herein, we made a collective literature review of reported cases of collision tumors composed of oncocytoma and papillary RCC, adding a case that we recently experienced. MATERIAL AND METHODS: A PubMed database was search for collision tumors of the kidney composed of oncocytoma and papillary RCC and a collective literature review was made. To this cohort, we also added a recently encountered case with similar, confirmed by immunohistochemistry, morphological features. RESULTS: To date 8 cases of a collision tumor composed of papillary RCC and oncocytoma have been described in the literature. All of them had a smaller papillary RCC component present within a larger oncocytoma. CONCLUSION: Because of a few cases of such a collision tumors reported, it is difficult to make classification and right clinical management of these patients. None of the reported cases had tumor recurrence or progression on a follow-up. The presence of only small portion of papillary RCC in a large oncocytoma raises a possibility of under-sampling of malignant component in large oncocytomas in core biopsy or surgically resected specimens. We recommend better sampling, particularly at the periphery of otherwise classic oncocytomas to unveil this possible association.

Sarcoid-like granulomas in renal cell carcinoma: The Houston Methodist Hospital experience.

Sarcoid-like (SL) granulomas have been previously described in association with malignant tumors. These granulomas appear to be tumor-related but are not indicative of systemic sarcoidosis, and hence are referred to as SL reactions. These SL reactions can be seen within the primary tumor, its vicinity, or in uninvolved sites such as the spleen, bone marrow, skin, and/or regional lymph nodes draining the tumor. It is a widely held view that SL granulomas are caused by soluble antigenic factors, shed by tumor cells or released due to tumor necrosis. SL reactions reported in Hodgkin lymphoma have been associated with a better prognosis. SL granulomas are thought to play an important role in the host's defenses against metastatic extension. SL granulomas have been reported in approximately 4.4% of carcinomas. Isolated cases of renal cell carcinoma (RCC) with SL granulomas have been reported with questionable prognostic significance. We identified 11 cases of RCCs with SL granulomas. Interestingly, all cases had abundant clear cell cytoplasm (10 clear cell RCC cases and 1 clear cell papillary RCC). We propose that this clear, abundant cytoplasm of the tumor cells with high content of glycogen and lipids may trigger granuloma formation akin to that seen in seminomas with SL granulomas. To date, this is the largest case series of RCCs with SL granulomas.

An isolated inflammatory myofibroblastic tumor of adrenal gland.

Inflammatory myofibroblastic tumor (IMT) is an uncommon lesion that shows a wide range of anatomic distribution. The adrenal gland, however, is a distinctly rare site of occurrence. To date, only a few cases of IMT arising in the adrenal gland have been reported in the English literature. Here, we report another case of isolated adrenal IMT. A 34-year-old man presented to the emergency department with a complaint of a sudden severe right-sided back pain. Subsequent computed tomographic scan imaging studies demonstrated a large right adrenal mass associated with a hematoma. The right adrenal gland was resected. Microscopic examination revealed an encapsulated cellular spindle cell proliferation with a prominent inflammatory infiltrate. Immunohistochemically, those spindle cells were diffusely and strongly positive for anaplastic lymphoma kinase-1, and focally and weakly positive for smooth muscle actin. S-100 protein and cytokeratin were negative. The findings were consistent with IMT arising from the adrenal gland. Although IMTs in the adrenal gland are rare, they should be considered in the differential diagnosis of adrenal masses. The clinical behavior of IMTs in general is currently indeterminate and a close clinical follow-up is recommended. The behavior of adrenal IMTs remains uncertain because of rare reported cases and lack of long-term follow-up. Further follow-up of reported cases and recognition of additional new cases is warranted to unmask the true biological behavior of adrenal IMTs.

Measuring Particulate Emissions of Light Duty Passenger Vehicles Using Integrated Particle Size Distribution (IPSD).

The California Air Resources Board (ARB) adopted the low emission vehicle (LEV) III particulate matter (PM) standards in January 2012, which require, among other limits, vehicles to meet 1 mg/mi over the federal test procedure (FTP). One possible alternative measurement approach evaluated to support the implementation of the LEV III standards is integrated particle size distribution (IPSD), which reports real-time PM mass using size distribution and effective density. The IPSD method was evaluated using TSI's engine exhaust particle sizer (EEPS, 5.6-560 nm) and gravimetric filter data from more than 250 tests and 34 vehicles at ARB's Haagen-Smit Laboratory (HSL). IPSD mass was persistently lower than gravimetric mass by 56-75% over the FTP tests and by 81-84% over the supplemental FTP (US06) tests. Strong covariance between the methods suggests test-to-test variability originates from actual vehicle emission differences rather than measurement accuracy, where IPSD offered no statistical improvement over gravimetric measurement variability.

Comparison of particle mass and solid particle number (SPN) emissions from a heavy-duty diesel vehicle under on-road driving conditions and a standard testing cycle.

It is important to understand the differences between emissions from standard laboratory testing cycles and those from actual on-road driving conditions, especially for solid particle number (SPN) emissions now being regulated in Europe. This study compared particle mass and SPN emissions from a heavy-duty diesel vehicle operating over the urban dynamometer driving schedule (UDDS) and actual on-road driving conditions. Particle mass emissions were calculated using the integrated particle size distribution (IPSD) method and called MIPSD. The MIPSD emissions for the UDDS and on-road tests were more than 6 times lower than the U.S. 2007 heavy-duty particulate matter (PM) mass standard. The MIPSD emissions for the UDDS fell between those for the on-road uphill and downhill driving. SPN and MIPSD measurements were dominated by nucleation particles for the UDDS and uphill driving and by accumulation mode particles for cruise and downhill driving. The SPN emissions were ∼ 3 times lower than the Euro 6 heavy-duty SPN limit for the UDDS and downhill driving and ∼ 4-5 times higher than the Euro 6 SPN limit for the more aggressive uphill driving; however, it is likely that most of the "solid" particles measured under these conditions were associated with a combination release of stored sulfates and enhanced sulfate formation associated with high exhaust temperatures, leading to growth of volatile particles into the solid particle counting range above 23 nm. Except for these conditions, a linear relationship was found between SPN and accumulation mode MIPSD. The coefficient of variation (COV) of SPN emissions of particles >23 nm ranged from 8 to 26% for the UDDS and on-road tests.

Characterization of particulate matter emissions from a current technology natural gas engine.

Experiments were conducted to characterize the particulate matter (PM)-size distribution, number concentration, and chemical composition emitted from transit buses powered by a USEPA 2010 compliant, stoichiometric heavy-duty natural gas engine equipped with a three-way catalyst (TWC). Results of the particle-size distribution showed a predominant nucleation mode centered close to 10 nm. PM mass in the size range of 6.04 to 25.5 nm correlated strongly with mass of lubrication-oil-derived elemental species detected in the gravimetric PM sample. Results from oil analysis indicated an elemental composition that was similar to that detected in the PM samples. The source of elemental species in the oil sample can be attributed to additives and engine wear. Chemical speciation of particulate matter (PM) showed that lubrication-oil-based additives and wear metals were a major fraction of the PM mass emitted from the buses. The results of the study indicate the possible existence of nanoparticles below 25 nm formed as a result of lubrication oil passage through the combustion chamber. Furthermore, the results of oxidative stress (OS) analysis on the PM samples indicated strong correlations with both the PM mass calculated in the nanoparticle-size bin and the mass of elemental species that can be linked to lubrication oil as the source.

A study of metastatic carcinoma found in hernia sacs between 2006 and 2012 at one institution.

Hernia sacs are generally regarded as routine specimens in the daily practice of surgical pathology. However, unexpected findings including carcinoma can occasionally arise in these seemingly benign specimens. To ascertain the prevalence of metastatic carcinoma found within hernia sacs and to determine the importance of routine histologic examination of hernia sacs, we conducted a retrospective study of all hernia sacs with a diagnosis of metastatic carcinoma reported in our hospital system between January 2006 and December 2012. Of 3117 total herniorrhaphy specimens between 2006 and 2012, 11 (0.35%) were found to have metastatic carcinoma. Interestingly, in 3 cases, the initial diagnosis of cancer was made during histologic examination of the hernia sac. Metastatic carcinoma in hernia sacs is a rare occurrence; however, it is encountered in routine practice. It is recommended that herniorrhaphy specimens not be discarded and, instead, be regarded as peritoneal biopsies for routine histologic examination.