False positive diagnosis of malignancy in a case of cryptogenic organising pneumonia presenting as a pulmonary mass with mediastinal nodes detected on fluorodeoxyglucose-positron emission tomography: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report the case of a patient with positive findings on a lung emission tomography/computed tomography (PET/CT) scan, with possible contra lateral mediastinal involvement, which strongly suggested an inoperable lung carcinoma. The lung mass proved to be a cryptogenic organising pneumonia. While the latter has previously been shown to be PET/CT positive, mediastinal involvement simulating malignant spread has not been previously reported.</p> <p>Case presentation</p> <p>A 50-year-old Caucasian woman presented with a history of unproductive cough and was found to have a mass in the right upper lobe as shown on chest X-ray and a computed tomography scan. A subsequent PET/CT scan showed strong uptake in the right upper lobe (maximum standard uptake values (SUVmax) 9.6) with increased uptake in the adjacent mediastinum and contralateral mediastinal nodes. Surgical resection and mediastinoscopy revealed cryptogenic organising pneumonia, with enlarged reactive mediastinal lymph nodes.</p> <p>Conclusion</p> <p>The case illustrates the limits of PET/CT scanning as a diagnostic tool, and emphasizes the importance of obtaining histological confirmation of malignant diseases whenever possible.</p

Translating microcalcification biomarker information into the laboratory: a preliminary assessment utilizing core biopsies obtained from sites of mammographic calcification

The potential of breast microcalcification chemistry to provide clinically valuable intelligence is being increasingly studied. However, acquisition of crystallographic details has, to date, been limited to high brightness, synchrotron radiation sources. This study, for the first time, evaluates a laboratory-based system that interrogates histological sections containing microcalcifications. The principal objective was to determine the measurement precision of the laboratory system and assess whether this was sufficient to provide potentially clinical valuable information. Materials and methods Sections from 5 histological specimens from breast core biopsies obtained to evaluate mammographic calcification were examined using a synchrotron source and a laboratory-based instrument. The samples were chosen to represent a significant proportion of the known breast tissue, mineralogical landscape. Data were subsequently analysed using conventional methods and microcalcification characteristics such as crystallographic phase, chemical deviation from ideal stoichiometry and microstructure were determined. Results The crystallographic phase of each microcalcification (e.g., hydroxyapatite, whitlockite) was easily determined from the laboratory derived data even when a mixed phase was apparent. Lattice parameter values from the laboratory experiments agreed well with the corresponding synchrotron values and, critically, were determined to precisions that were significantly greater than required for potential clinical exploitation. Conclusion It has been shown that crystallographic characteristics of microcalcifications can be determined in the laboratory with sufficient precision to have potential clinical value. The work will thus enable exploitation acceleration of these latent microcalcification features as current dependence upon access to limited synchrotron resources is minimized.This work was supported by a Medical Research Council research grant MR/T000406/1 that funded the conduct of the research and preparation of the article

Anisotropy visualisation from X-ray diffraction of biological apatite in mixed phase calcified tissue samples

X-ray diffraction is widely used to characterise the mineral component of calcified tissue. Broadening of the diffraction peaks yields valuable information on the size of coherently diffracting domains, sometimes loosely described as crystallite size or crystallinity. These domains are markedly anisotropic, hence a single number describing their size is misleading. We present a novel variation on a method for visualising crystallographic anisotropy in X-ray diffraction data. This provides an intuitively interpretable depiction of crystalline domain size and anisotropy. The new method involves creating a polar plot of calculated domain thickness for peaks in a diffractogram versus crystallographic direction. Points with the least error are emphasised. Anisotropic domain dimensions are calculated by refining an ellipsoidal model in a whole pattern fit. These dimensions are then used to overlay an ellipse on the peak broadening plot. This is illustrated by application of the method to calcifications in breast tissue with suspected cancer, which frequently contain whitlockite as well as nanocrystalline apatite. Like most biogenic apatite, this exhibits markedly anisotropic peak broadening. The nature of this anisotropy offers potentially useful information on normal function and pathology of calcified tissue and is a frequently neglected crystallographic feature of these materials.This work was supported by a Medical Research Council research grant MR/T000406/1 that funded the conduct of the research and preparation of the article. We thank Diamond Light Source for access to beamline I18 under proposal number sp30215-1.Scientific Report

A multi-modal exploration of heterogeneous physico–chemical properties of DCIS breast microcalcifications

Ductal carcinoma in situ (DCIS) is frequently associated with breast calcification. This study combines multiple analytical techniques to investigate the heterogeneity of these calcifications at the micrometre scale. X-ray diffraction, scanning electron microscopy and Raman and Fourier-transform infrared spectroscopy were used to determine the physicochemical and crystallographic properties of type II breast calcifications located in formalin fixed paraffin embedded DCIS breast tissue samples. Multiple calcium phosphate phases were identified across the calcifications, distributed in different patterns. Hydroxyapatite was the dominant mineral, with magnesium whitlockite found at the calcification edge. Amorphous calcium phosphate and octacalcium phosphate were also identified close to the calcification edge at the apparent mineral/matrix barrier. Crystallographic features of hydroxyapatite also varied across the calcifications, with higher crystallinity centrally, and highest carbonate substitution at the calcification edge. Protein was also differentially distributed across the calcification and the surrounding soft tissue, with collagen and β-pleated protein features present to differing extents. Combination of analytical techniques in this study was essential to understand the heterogeneity of breast calcifications and how this may link crystallographic and physicochemical properties of calcifications to the surrounding tissue microenvironment.Cancer Research UK and by KWF Kankerbestrijding: C38317/A2404

Microcalcification Crystallography as a Potential Marker of DCIS Recurrence

Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation

Microcalcification crystallography as a potential marker of DCIS recurrence

Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation. [Abstract copyright: © 2023. The Author(s).

Screening detects a myriad of breast disease – refining practice will increase effectiveness and reduce harm

For many individuals, the term ‘cancer’ equates to a disease that if untreated will progress, spread from the area initially affected and ultimately cause death. ‘Breast cancer’, however, is a diverse of range of pathological entities, incorporating indolent to fast-growing and aggressive lesions, with varying histological patterns, clinical presentations, treatment responses and outcomes. Screening for malignancy is based on the assumption that cancer has a gradual, orderly progression and that detecting lesions earlier in their natural history, and intervening, will reduce mortality. The natural history of epithelial atypia, ductal carcinoma in situ and even invasive breast cancer is poorly understood, but widely variable. We believe that population breast screening methodology needs to change to focus on diagnosis of lesions of greatest clinical relevance. </jats:p