Pathologist Computer-Aided Diagnostic Scoring of Tumor Cell Fraction: A Swiss National Study.

Tumor cell fraction (TCF) estimation is a common clinical task with well-established large interobserver variability. It thus provides an ideal test bed to evaluate potential impacts of employing a tumor cell fraction computer-aided diagnostic (TCFCAD) tool to support pathologists' evaluation. During a National Slide Seminar event, pathologists (n = 69) were asked to visually estimate TCF in 10 regions of interest (ROIs) from hematoxylin and eosin colorectal cancer images intentionally curated for diverse tissue compositions, cellularity, and stain intensities. Next, they re-evaluated the same ROIs while being provided a TCFCAD-created overlay highlighting predicted tumor vs nontumor cells, together with the corresponding TCF percentage. Participants also reported confidence levels in their assessments using a 5-tier scale, indicating no confidence to high confidence, respectively. The TCF ground truth (GT) was defined by manual cell-counting by experts. When assisted, interobserver variability significantly decreased, showing estimates converging to the GT. This improvement remained even when TCFCAD predictions deviated slightly from the GT. The standard deviation (SD) of the estimated TCF to the GT across ROIs was 9.9% vs 5.8% with TCFCAD (P < .0001). The intraclass correlation coefficient increased from 0.8 to 0.93 (95% CI, 0.65-0.93 vs 0.86-0.98), and pathologists stated feeling more confident when aided (3.67 ± 0.81 vs 4.17 ± 0.82 with the computer-aided diagnostic [CAD] tool). TCFCAD estimation support demonstrated improved scoring accuracy, interpathologist agreement, and scoring confidence. Interestingly, pathologists also expressed more willingness to use such a CAD tool at the end of the survey, highlighting the importance of training/education to increase adoption of CAD systems.

[Panhypopituitarism, Diabetes Insipidus and Bone Pain - Is There a Systemic Disease Behind it?]

INTRODUCTION: A 27-year-old man presented due to unilateral leg pain. He had a history of diabetes insipidus and panhypopituitarism. Laboratory analysis revealed hormonal undersupply. MRI showed a large contrast medium-absorbing mass in the pituitary gland extending into the hypothalamus. FDG-PET/CT examination revealed a hypermetabolic soft tissue lesion around the left femoral shaft. After biopsy of the lesion, a diagnosis of multisystemic Langerhans cell histiocytosis was made.

Fourier-transform infrared spectroscopy imaging is a useful adjunct to routine histopathology to identify failure of polyethylene inlays in revision total hip arthroplasty.

The use of highly crosslinked ultra-high molecular weight polyethylene (XLPE) has significantly reduced the volumetric wear of acetabular liners, thereby reducing the incidence of osteolysis. However, contemporary components tend to generate smaller wear particles, which can no longer be identified using conventional histology. This technical limitation can result in imprecise diagnosis. Here, we report on two uncemented total hip arthroplasty cases (~7 years in situ) revised for periprosthetic fracture of the femur and femoral loosening, respectively. Both liners exhibited prominent wear. The retrieved pseudocapsular tissue exhibited a strong macrophage infiltration without microscopically identifiable polyethylene particles. Yet, using Fourier-transform infrared micro-spectroscopic imaging (FTIR-I), we demonstrated the prominent intracellular accumulation of polyethylene debris in both cases. This study shows that particle induced osteolysis can still occur with XLPE liners, even under 10 years in situ. Furthermore, we demonstrate the difficulty of determining the presence of polyethylene debris within periprosthetic tissue. Considering the potentially increased bioactivity of finer particles from XLPE compared to conventional liners, an accurate detection method is required, and new histopathological hallmarks of particle induced osteolysis are needed. FTIR-I is a great tool to that end and can help the accurate determination of foreign body tissue responses.

Pleural Effusion Caused by an Unusual Mass in the Right Hemithorax.

CASE PRESENTATION: An 80-year-old woman presented with complaints of weakness and dizziness. She had a medical history of subacute cerebral ischemia, vertigo, hypertension, and thalassemia minor. The patient was born and raised in Turkey and has lived in Switzerland for 50 years. Her sister died of a mesothelioma caused by asbestos exposure at the age of 60 years but had lived in Turkey until her death. The patient had neither a history of TB nor B symptoms. She has never smoked.

Mucin-producing adenocarcinoma arising in an atrial myxoma.

We describe the unique autopsy findings of a patient who died of a metastasizing giant right atrial adenocarcinoma containing few areas of typical myxoma. That no mucin-producing extracardiac tumor was detected pointed to the atrial adenocarcinoma as being the primary. We hypothesize that the adenocarcinoma may have developed from coexistent bland glandular structures within the myxoma.

[A Rare Diagnosis for a Patient with Shoulder Pain - Mature Teratoma of the Mediastinum]. / Seltene Diagnose für einen Patienten mit Schulterschmerzen: reifes Teratom des Mediastinums.

INTRODUCTION: Thanks to a conscientious work-up in the general practitioner's office and referral to goal-directed diagnostics, the benign thoracic tumor could be submitted to curative resection. Although the radiological and laboratory examinations made the benign entity of a mature teratoma in a young, postpubertal male highly probable, the clinic is usually nonspecific and makes classification difficult, so that a histo-pathological work-up and resection were mandatory in this case in order to obtain diagnostic certainty about the dignity and to allow for timely therapy according to the guidelines.

Early failure of a highly cross-linked polyethylene inlay after total hip arthroplasty probably due to insufficient irradiation.

Highly cross-linked polyethylene (XLPE) is a major advance in total hip arthroplasty (THA), as it suffers from less wear and thus is associated with lower revision rates than standard ultra-high molecular weight polyethylene. Early failures are reported rarely, and associated with specific design or manufacturing issues. We report a case requiring early revision due to adverse reaction to polyethylene particles. Investigations identified insufficient irradiation as the most probable cause of failure. Here are reported the features of a clinical case with determination of the material properties of the retrieved XLPE liner and establishment of the appropriate calibration curves as reference. Periprosthetic joint infection could be ruled out with appropriate sampling as cause for the inflammatory periarticular tumour. Histology identified a massive macrophagic reaction to micrometric polyethylene particles. No component malposition was present, nor any third-body wear. The trans-vinylene index (TVI) indicated insufficient and potentially detrimental irradiation of the polyethylene, while gel content, crystallinity, melting temperature and oxidation index remained within expected ranges. Histologically proven failure of a XLPE THA liner was identifiable despite correct implantation of the components. The cause of failure most probably was an inadequate irradiation, as indicated by determination of the TVI. This case underscores the importance of histologic workup even in aseptic revisions, and of detailed analysis of retrievals. The calibration curves provided are essential for analysis of other retrievals.

It's worth cleaning - The examination of the female taper could identify a particular cause of trunnionosis at revision 16 years after total hip arthroplasty.

Adverse reaction to metal debris (ARMD) is an issue in metal-on-metal (MoM) total hip replacements (THR). It mainly affects large-head MoM THR, whereas 28-32 mm MoM pairings are associated with low long-term revision rates. However, the bearing surface is not necessarily the only cause of metal debris. This report documents with advanced analysis of the retrievals a particular cause of trunnionosis in late failure of a small diameter MoM THR and illustrates the importance of cleaning of the taper when seating the head in THR. A 65-year-old patient was revised due to ARMD 16 years after small diameter MoM THR. Debridement and exchange of the inlay and the head had been performed through an anterior approach. While the cup and the outer surface of the head were accessible to direct analysis by an optical coordinate measuring machine, the female taper had to be analysed indirectly by measuring an imprint. Wear from the cup and the head was within expected low ranges. The analysis of the female taper identified bone fragments, which contributed to trunnionosis. Failure due to ARMD after MoM THR is not necessarily caused by the bearing, but can be due to trunnionosis. Bone fragments within the taper contact in this case highlight the importance of meticulous cleaning of the taper before seating the head, to avoid trunnionosis.

[Systemic disease with hepatic and pulmonary involvement]. / Systemerkrankung mit Leber- und Lungenbeteiligung.

We discuss the history of a 39 year old woman with multiple patchy consolidations on high - resolution computed tomography in combination with a delayed diagnosis of primary biliary cirrhosis. Further we review the differential diagnostic considerations and step by step diagnostic and therapeutic options. Based on the presentation with symptoms of a mitigated pneumonia at the beginning of the disease, the differential diagnosis of cryptogenic organising pneumonia (CO) is discussed. The diagnosis of COP is often delayed. The theoretic background of primary biliary cirrhosis and the association with pulmonary disease are broadly discussed.

New Insights into Osteointegration and Delamination from a Multidisciplinary Investigation of a Failed Hydroxyapatite-Coated Hip Joint Replacement.

Hydroxyapatite (HA) coatings have become very popular in uncemented total hip arthroplasty (THA). Analysis of retrievals and tissue samples from an HA-coated femoral stem, which failed within 14 months after THA, provides exceptional insights into the failure mechanism, as well as the process of osteointegration of such an implant. METHODS: Retrievals were photo-documented. Samples were examined by micro-computed tomography, X-ray diffraction (XRD) and embedded in polymethylmethacrylate for histology. RESULTS: The coating had partially delaminated. The sandblasted surface of the stem was partially polished by the delaminated HA coating, indicating failure before revision. In the tissue samples, the HA coating was well integrated by newly formed bone trabeculae. No adverse biological reaction was observed. XRD analysis showed that residues of the HA coating were still present and could clearly be differentiated from the surrounding bone. Preferential orientation of the HA crystallites could be identified within the newly formed bone, representing a potential mechanical weakness induced either by physiologic strain or by the coating. CONCLUSION: current HA coatings, relatively thick and made of high crystallinity HA, may be prone to delamination, as also seen in our study. Recent efforts have aimed towards thinner (<1 µm) coatings with nanocrystalline HA structures that possibly relate to lower delamination risks. However, the question arises if HA coatings are beneficial since sandblasted non-coated stems offer similar results without the risk of delamination. XRD not only permits differentiation between the HA from the coating and the HA of the ongrown bone, it also provides new insights into the microstructure of this newly formed bone.

Sclerosing angiomatoid nodular transformation (SANT) of the spleen: sonographic finding.

Sclerosing angiomatoid nodular transformation (SANT) is a recently recognized benign vascular lesion of the spleen. There is limited information regarding its imaging findings of this condition. Until now, the diagnosis was based on histopathologic examination of splenectomy specimens. We report the sonographic findings in a case of SANT of the spleen confirmed by ultrasound-guided core needle biopsy.

Chromosomal translocations t(4;14), t(11;14) and proliferation rate stratify patients with mature plasma cell myelomas into groups with different survival probabilities: a molecular epidemiologic study on tissue microarrays.

Plasma cell myelomas (PMs) exhibit clinical and molecular heterogeneity. To date, morphology and immunohistochemistry on bone marrow trephines are of limited value to stratify patients into different prognostic categories. However, some chromosomal translocations are of prognostic and/or of predictive importance in PMs. In this study, the prognostic significance of morphology, CyclinD1 expression, proliferation index (Mib1) and presence of the translocations FGFR3/IgH [t(4;14)] and CCND1/IgH [t(11;14)] are compared in 119 patients with PM. Immunohistochemistry and fluorescence in situ hybridization analysis were carried out on a tissue microarray containing bone marrow trephines. Hundred and one PMs showed a mature morphology whereas 10 were immature. All but one PM carrying a translocation showed a mature morphology. Patients with a t(4;14) (12%) had a statistically significant shorter 1-year survival (P=0.004), whereas those with a t(11;14) (21%) had a trend towards a better clinical outcome. CyclinD1 protein expression was not significantly associated with survival. Besides the t(4;14), an immature morphology (P<0.001) and a proliferation index (Mib1) of more than 10% (P=0.002) were associated with a significantly worse outcome. A high occurrence of strong CyclinD1 protein expression in the tumor cells was predictive of either a t(11;14) or of a low level amplification of the CCND1 gene, suggesting that different molecular mechanisms may have lead to an over-expression of the CyclinD1 protein in PMs. These findings demonstrate that a high proliferation rate and translocations involving the IgH locus can stratify mature PMs into groups with distinct survival probabilities.

IgM multiple myeloma with an extremely rare non-aggressive presentation: A case report.

In the present study, the case of a 41-year-old man with immunoglobulin (Ig)M multiple myeloma (MM) that presented with an unusually non-aggressive clinical course who has survived for >9 years to date, is presented. Initial diagnosis of symptomatic MM was established according to the International Myeloma Working Group consensus statement and guidelines. Due to the mild symptoms, no therapy was administered and the patient was closely followed up. Eight years after initial diagnosis, clinical, morphological and genetic progression occurred with the development of hypercalcemia, progressively deteriorating polyneuropathy, clonal expansion of plasma cells up to 50% of hematopoietic cells and demonstration of the typical t(11;14) translocation (Ig heavy chain locus rearrangement). Subsequently, 4 cycles of induction chemotherapy with velcade, cyclophosphamide and dexamethasone, were administered. At the time of writing, the patient remained alive in generally good health. To the best of our knowledge, with a survival time of >9 years, this case reports the longest survival time of an IgM MM patient to date, which contradicts previous evidence that suggests IgM MM exhibits an aggressive clinical course.

Benign atypical intravascular CD30+ T-cell proliferation: a recently described reactive lymphoproliferative process and simulator of intravascular lymphoma: report of a case associated with lichen sclerosus and review of the literature.

OBJECTIVES: Intravascular accumulations of atypical large lymphoid cells are a rare finding in skin biopsy specimens and raise the suspicion for intravascular lymphoma. The intravascular accumulation of atypical large CD30+ T cells, however, as a reactive process is very uncommon in the skin, with only four cases documented so far in the literature. This condition, referred to as benign intravascular atypical CD30+ T-cell proliferation, has been associated with chronic inflammation after trauma. METHODS: We report on a case of atypical intravascular CD30+ T-cell proliferation in a patient with ulcerated lichen sclerosus on the foreskin, discuss the differential diagnoses, propose diagnostic criteria, and review the literature on this uncommon reactive intralymphatic CD30+ T-cell lymphoproliferation. RESULTS: The atypical intravascular CD30+ T-cell proliferation is characterized by the accumulation of large CD30+ polyclonal T cells within lymphatics in close vicinity to ulceration or an inflammatory skin disease. There is no association with Epstein-Barr virus infection. CONCLUSIONS: This benign cutaneous lymphoproliferation needs to be distinguished from intravascular T-cell lymphoma, particularly from the intravascular variant of anaplastic large cell lymphoma. Obstruction of lymphatics due to lichen sclerosus with disrupted immune cell trafficking may result in the accumulation of activated CD30+ lymphocytes.

How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss Working Group of Breast- and Gynecopathologists.

UNLABELLED: Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas. METHODS: Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later. RESULTS: The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56-0.72). However, we found very high inter-observer variabilities (Kappa 0.04-0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01-0.04) and intra-observer agreement was likewise poor (Kappa 0.00-0.35). CONCLUSION: Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas.

Cystic dysplasia of the testis: a very rare paediatric tumor of the testis.

OBJECTIVES: To describe a case of cystic dysplasia of the testis (CDT), an uncommon cause of scrotal swelling in the pediatric patient. Clinic, therapy, fertility, and radiographic and pathologic findings are discussed and the 30 previously reported cases are reviewed. METHODS: A 9-year-old boy presented with asymptomatic scrotal swelling. A scrotal ultrasound showed a multicystic scrotal mass in the rete testis and an ipsilateral renal agenesis. The growth in size of the mass forced the authors to perform an operative exploration. RESULTS: Intraoperative findings included a multicystic mass in the rete testis of the right testicle. Testicle-sparing total removal of the multicystic mass was performed and the pathologic examination revealed a benign, multilobulated configuration of the cysts in the region of the rete testis. These findings were similar to those found in previously reported cases of CDT. Ipsilateral renal agenesis is the most common associated anomaly. As a pathogenetic factor, mal-junction of the Wolffian duct in the 5th week of gestation is most creditable. CONCLUSIONS: CDT is a rare cause of pediatric scrotal mass. When feasible, a testicle-sparing approach should be considered and all patients should undergo evaluation for associated urologic anomalies.

Giant cardiac myxoma with malignant transformed glandular structures.

A case of a right-sided giant cardiac myxoma with malignant transformation of glandular structures causing systemic metastases is described. Plain chest radiography and computed tomography localized the tumor within the heart. Exact depiction of the origin of the tumor using subtracted 2D-projection MR angiography is documented. Radiologic findings and differential diagnosis of this unique tumor are discussed.